Sarcomas Flashcards
SDH deficient GIST
Insensitive to imatinib- use sunitinib or regorafenib
Localized, clinically resectable, extremity and superficial trunk soft tissue sarcoma
(Tx overview)
Grade 1: surgery +/- radiation
Grade 2-3: surgery +/- radiation and chemo before and after surgery
Localized, clinically unresectable, extremity and superficial trunk soft tissue sarcoma
(Tx overview)
Neoadjuvant chemo +/- RT
—-> surgery if now resectable, otherwise tx as advance dx
Advanced/metastatic clinically resectable soft tissue sarcoma
(Tx overview)
Isolated Mets: surgery +/- chemo
Mx Mets: tx as advance unresectable
Advanced/metastatic, unresectable soft tissue sarcoma
(Non-specific histology)
Chemo, options are:
1. Doxorubicin (better for less fit patients)
2. Doxorubicin + ifos + Mesna (AIM)
*give with g-CSF
Others:
-doxorubicin + Dacarbazine (AD)
- ifos + Epirubicin + Mesna
-liposomal dox
-Epirubicin
Advanced/metastatic, unresectable soft tissue sarcoma
(Non-specific histology)
And cannot tolerate doxorubicin
Gemcitabine + docetaxel (or Vinorelbine or dacarbazine)
infuse Gemcitabine at 10 mg/m2/min -increases efficacy has not been proven but this is how it was studied
Advanced/metastatic, unresectable soft tissue sarcoma. non-liposomal
(Non-specific histology)
SECOND LINE
Pazopanib
Advanced/metastatic, unresectable soft tissue sarcoma. Liposomal
(Non-specific histology)
Eribulin or trabectedin
(use 2 lines of therapy first including anthracycline)
Advanced/metastatic, unresectable soft tissue sarcoma. Leimyosarcoma.
(Non-specific histology)
Trebectedin
Soft tissue sarcoma neoadjuvant
Dox + ifos + Mesna (AIM)
(Or Epirubicin instead of dox)
*give with g-CSF
Soft tissue sarcoma neoadjuvant
Unable to do doxorubicin
Gemcitabine + docetaxel
Soft tissue sarcoma: Desmoid tumors (aggressive fibromatosis)
Observation!!!
-Sorafenib (cat 1)
-nirogacestat (cat 1)
Others:
-Mtx + vin
-imatinib
-liposomal dox
-dox + Dacarbazine
-Pazopanib
Associated with Gardner syndrome (APC gene mutation)
Soft tissue sarcoma: non-pleomorphic rhabdomyosarcoma
Vincristine + dactinomycin + cyclophosphamide (VAC)
Soft tissue sarcoma: alveolar soft part sarcoma
-sunitinib
-Pazopanib
-pembrolizumab
-pembro + axitinib
-atezolizumab
Soft tissue sarcoma: angiosarcoma
Paclitaxel
Or doxorubicin
Soft tissue sarcoma: dermatofibrosarcoma transformation (DFSP)
Imatinib
Soft tissue sarcoma: Epithelioid sarcoma
Early stage: surgical resection
Metastatic: Tazometostat 800 PO BID
Extra skeletal osteosarcoma
-ifos
- or doxorubicin + cisplatin
“I am a CD”
Dedifferentiated chordoma
Treat as general soft tissue sarcoma (anthracycline OR Gemcitabine based regimens )
Soft tissue sarcoma: inflammatory myofibroblastic tumor (IMT) with anaplastic lymphoma kinase (ALK) translocation
-alectinib
-Brigatinib
-ceritinib
-crizotinib
-lorlatinib
Soft tissue sarcoma: malignant perivascular epitheloid cell tumor (PEComa)
Albumin based sirolimus
Recurrent angiomyolipoma
OR
lymphangioleiomyomatosis
-sirolimus
-everolimus
-temsirolimus
Soft tissue sarcoma: solitary fibrous tumor
-bevacizumab + temozolomide
-sunitinib
-sorafenib
-pazopanib
Tenosynovial giant cell tumor/pigmented villonodular synovitis
Pexidartinib
Retroperitoneal well differentiated or dedifferentiated liposarcoma
Palbociclib
Soft tissue sarcoma: uterine leiomyosarcoma
Gemcitabine + docetaxel
Myxoid liposarcoma
-dox
-dox + dacarbazine (AD)
Soft tissue sarcoma: pleomorphic liposarcoma
Doxorubicin
Synovial sarcoma
Doxorubicin + ifos
afamitresgene autoleucel
Bone sarcoma: giant cell tumor of bone
First line: surgery or serial arterial embolization
RT if recurrence or inoperable
Denosumab
-interferon/peginterfeuron can be options
Bone sarcoma: osteosarcoma
Neoadjuvant/adjuvant or metastatic
First line
If >40 y/o: cisplatin + doxorubicin
If <40 y/o: high dose MTX (12 g/m2) + cisplatin + doxorubicin (MAP)
neoadjuvant *2-6 cycles—>surgery —>
Adjuvant 2-12 cycles
MTX 12 g/m2!!!- probably cap at 20 g!!!
Same regimens used for metastatic just no surgery
Bone sarcoma: osteosarcoma
Second line or relapsed/refractory
-Ifosfamide (high dose) +/- etoposide (cat 2A)
-regorafenib (cat 1)!!
-sorafenib (cat 2A)
Bone sarcoma: Ewing sarcoma
First line: adjuvant/Neoadjuvant/primary)
-NEOADJUVANT!!! vincristine + doxorubicin + cyclophosphamide alternating with ifosfamide + etoposide (VDC/IE)- every 2 weeks
*give with g-CSF
-surgery after chemo
-very radiosensitive but RT reserved for when we can’t do surgery
-follow with adjuvant chemo
Metastatic
-HD-chemo—>ASCT
Bone sarcoma: Ewing sarcoma
Primary therapy
-Surgery and neoadjuvant/adjuvant chemo (RT option if can’t do surgery- radiosensitive but toxicities)
-Vincristine + dox + cyclophosphamide alternative w/ ifos + etop (VDC/IE)- every 2 weeks
-vincristine + dox + ifos + dactinomycin (VAIA)
-vincristine + ifos + dox + etoposide (VIDE)
-vincristine + dox + cyclophosphamide (VDC)
*give these with g-CSF
*neoadjuvant, can also do adjuvant
Bone sarcoma: Ewing sarcoma
Second line for relapsed refractory or metastatic dx
-Cyclophosphamide + topotecan
-irinotecan + temozolomide +- vincristine
Bone sarcoma: chordoma
-primary therapy is surgery
-if unresectable- RT is primary therapy
-imatinib
-dasatinib
-sunitinib
Dedifferentiated should be tx as STS
Sarcoma: GIST
Neoadjuvant for resectable dx
KIT or PDGFRA (except exon 18 including D842V)
-Imatinib
-Note: no proven role for neoadjuvant at this time, usually adjuvant for 1-3 years
PDGFRA exon 18 D842V mutation
-Avapritinib 300 mg daily on empty stomach
Sarcoma: GIST
Neoadjuvant, resectable or metastatic
NTRK gene fusionpositive
-larotrectinib
-entrectinib
FOR FUSIONS, NOT MUTATIONS
Sarcoma: GIST
Neoadjuvant, resectable dx or metastatic
SDH deficient
Sunitinib
Sarcoma: GIST
Neoadjuvant, resectable, or metastatic
BRAF V600E mutated
Dabrafenib + trametinib
Sarcoma: GIST Resectable
Adjuvant therapy
High risk: imatinib x3 yr
Low risk: imatinib x 1yr
400 mg daily
Note: for resectable dx usually adjuvant not neoadjuvant
Sarcoma: GIST metastatic
First line: Imatinib
Second line: sunitinib
Third line: regorafenib
Fourth line: ripretinib
PDGFRA exon 18 mutation including PDGFRA D842V- Avapritinib (notice also used as neoadjuvant in resectable dx)
Sarcoma: GIST metastatic
Exon 9 mutation
Imatinib 800 mg/day 400 mg BID
Sarcoma: GIST
PDGFRA exon 18 mutation including PDGFRA D842V
Avapritinib- neoadjuvant if resectable and also for metastatic/unresectable
Second line: dasatinib
WHO grade II glioma (astrocytoma, or oligodendroglioma)
Initial tx
Surgery —->RT—->PCV x6
(Procarbazine + lomustine + vincristine)
**(category 1 for high risk (>40 y or subtotal resection) **
Recurrent
Surgery again + RT and concurrent or adjuvant PCV or TMZ
-TMZ is alternative if pt can’t take PCV
-Ivosidenib if chemo not preffered and IDH mutated
Useful in certain circumstances: ivosidenib
Grade III oligodendroglioma- with co-deletion of 1p/19q
Surgery—>RT + neoadjuvant or adjuvant PCV (Category 1)
(Procarbazine + lomustine + vincristine)
TMZ is alternative if pt can’t take PCV
Useful in certain circumstances: ivosidenib
Grade III astrocytoma
Anaplastic astrocytoma?
Surgery—>RT + adjuvant TZM
Anaplastic: EBRT
Grade IV glioma
(Glioblastoma, IDH wildtype astrocytoma)
Surgery —>RT m-f + TMZ 75 mg/m2 QD—> month break
—>TMZ 150–>200 mg/m2 QD x 5d q28d x6 cycles (start at 150mg/m2)
-give pjp ppx with TMZ
-if >70 can use Hypofractionated RT
-if MGMT methylated and >70y and/or PFS<60: TMZ alone
-if MGMt methylated and <70y and KPS >60 can: RT + concurrent lomustine and TMZ
-+/- electric field therapy
-regardless of methylation status
Note: we often see pseudo progression in first 3 months due to tx with RT!!
Primary CNS lymphoma Induction
RMT
HD MTX 8 g/m2 + rituximab +/- TMZ
Consolidate with etoposide + Cytarabine +/- WBRT
Or
RMPV
HD MTX 3.5 g/m2 + rituximab + vincristine + Procarbazine
Consolidate with Cytarabine —>ASCT
Note: we give MTX as short infusion (not continuous) bc it actually doesn’t have great CNS penetration (hydrophilic) so we need high peak concentrations for it to diffuse through the CNS
Note:
-organ transplant pts- try tapering immunosuppressants to get spontaneous remission
-HIV pts- poor prognosis, give ART
Primary CNS lymphoma consolidation
Consider archiving this card (consolidation discussed on other pcnsl notecard)
HD systemic therapy w/ stem cell rescue
-Cytarabine + thiotepa—> carmustine + thiotepa
-thiotepa + busulfan + cyclophosphamide
-HD Cytarabine + etoposide
-HD Cytarabine
Adult medulloblastoma
Weekly vincristine during craniospinal RT —>
-cisplatin + cyclophosphamide + vincristine
Or
-cisplatin + lomustine + vincristine
Meningioma (benign)
No preferred regimen- usually just surgery —-> adjuvant RT
Systemic therapy only if anaplastic, or progression despite above tx
-bevacizumab (2A)
-sunitinib (2B)
-bevacizumab +/-everolimus (2B)
Non-muscle invasive bladder CA
(Tx overview)
TURBT—>intravesical BCG or chemo x1—>induction x1-2—> maintenance (for intermediate (1y) or high (3y) risk
Muscle invasive bladder CA (T2 or above)
(Tx overview )
TURBT—>Neoadjuvant cisplatin (dd-MVAC preferred) based chemo——->cystectomy—->adjuvant nivolumab? (For high risk: T3-4a or N+ and not eligible/declines adjuvant chemo)
-some patients can consider bladder sparing approach
-note: can do split cisplatin for borderline renal function (40 ml/min)
Metastatic bladder CA
(Tx overview)
Chemo. Immunotherapy. Targeted therapy
Can do in addition to local treatments or start with chemo alone. But note for non-metastatic chemo is typically neoadjuvant and followed by surgery unless trying to do bladder sparing approach
NMIBC- low risk
TURBT—>one immediate (within 24h, ideally 6h) instillation of intravesical chemo then observation
Low risk= Ta (low grade) solitary and </=3cm, no CIS (carcinoma in situ)
*intravesical chemo with Gemcitabine or mitomycin
Notice- using chemo here, not BCG
Recurrent or persistent
-can repeat induction x1, after that switch to a different agent
Note: muscularis MUCOSA is Non-muscle invasive (unlike muscularis propria)
NMIBC- intermediate risk
TURBT—> immediate intravesical chemo (NOT BCG) —>intravesical chemo for max 1 yr OR BCG x1 yr (start BCG 3-4 weeks after TURBT)
Note: BCG induction (weekly x6) for max 2 inductions (12 weeks)*, maintenance is x1yr
Intermediate=
Ta (low grade) recurrent, >3 cm, or multifocal;
Ta (high grade) <3cm
T1 low grade
*chemo w/ intravesical Gemcitabine or mitomycin
Notice, chemo or BCG acceptable here unlike with low/high risk
Recurrent or persistent
-can repeat induction x1, after that switch to a different agent
Note: muscularis MUCOSA is Non-muscle invasive (unlike muscularis propria)
NMIBC-high risk
TURBT——>BCG (start 3-4 weeks after TURBT) x3 yrs OR radical cystectomy (NO immediate intravesical therapy after surgery)
Note: BCG induction (weekly x6) for max 2 inductions (12 weeks), maintenance is x3 yr
High risk=
Ta (high grade): recurrent, >3cm, or multifocal
T1 (high grade)
Tis
notice, use BCG, NOT chemo for tumor is situ and high risk, may use mitomycin if unable to tolerate BCG for other high risk
Recurrent or persistent
-can repeat induction x1, after that switch to a different agent
Note: muscularis MUCOSA is Non-muscle invasive (unlike muscularis propria)
NMIBC- very high risk
Radical cystectomy OR BCG induction and 3 years of maintence
Highest risk=
-T1 G3/HG associated with concurrent bladder CIS
-mx and/or large T1 G3/HG and/or recurrent T1 G3/HG with CIS in the prostatic urethra
-some forms of variant histology or prostatic urothelial carcinoma, lymphovascular invasion
Note: muscularis MUCOSA is Non-muscle invasive (unlike muscularis propria)
High risk NMIBC- carcinoma in situ (CIS) who are BCG unresponsive and do not want radical cystectomy
-radical cystectomy (preferred)
-Pembrolizumab
Intravesical options
-valrubicin
-Gemcitabine
-nadifaragene firadenovec (select patients)
MIBC-not metastatic (stage II-III)
TURBT—>neoadjuvant ddMVAC (preferred, 3-6 cycles) OR GC (4 cycles) —>radical cystectomy w/ pelvic lymph node dissection
consider adjuvant ddMVAC if they didn’t get neoadjuvant, or *nivolumab- evidence not great for adjuvant (Dont confuse with avelumab in metastatic setting)
ddMVAC- dose sense MTX + Vinblastine + dox + cisplatin (must give w/ G-CSF)
GC- Gemcitabine + cisplatin
Do no sub cisplatin with Carboplatin for non-metastatic MIBC (better to just not give any chemo if can’t get cisplatin)
Note: ddMVAC probably preferred in this setting
Metastatic bladder cancer
Cisplatin eligible
Preffered
-Pembro + enfortumab vedotin
Other
-ddMVAC (mtx + Vinblastine + dox + cis)
OR
-GC (gem + cisplatin)
Above two FOLLOWED BY—> avelumab maintenance (if no progression w/ first line)
-GC (gem + cisplatin) + nivo —> nivo maintenance
Note: cisplatin eligibility:
-crcl>60
-ECOG PS 0 or 1
-adequate hearing
Metastatic bladder CA
Cisplatin ineligible
Preffered
-pembro + enfortumab vedotin
Other
Gemcitabine + Carboplatin
FOLLOWED BY avelumab
Metastatic bladder CA
Platinum ineligible
I THINK THIS CARD SHOULD BE ARCHIVED FOR NOW
-Pembrolizumab (platinum ineligible regardless of PD-L1 expression)
-pembro + enfortumab
-atezolizumab (cisplatin ineligible if PD-L >5%, or platinum ineligible regardless of PD-L1 status)
Metastatic bladder CA
2nd line
Prior chemo
Pembrolizumab (category 1) (notice preferable to give alone NOT with Enfortumab vedotin-combo is 2B)
Prior ICI-cisplatin eligible
-Gemcitabine + cisplatin
-ddMVAC
-erdifinitib (If FGFR2 or FGFR3 alterations)
Prior ICI- cisplatin ineligible
-enfortumab vedotin (2a, usually 3rd line)
-Gemcitabine + Carboplatin
-erdafitinib
can repeat platinum based therapy if PFS>12 months
Metastatic bladder CA
Third line
Enfortumab vedotin
Or erdafinitib if FGRF 2/3 mutation
Bladder CA radiosensitizing chemo regimens
-cisplatin alone
-low dose gemcitabine
-5-FU and mitomycin
Given with RT after TURBT for bladder preservation (or not cystectomy Candidate) with stage II and IIIa MIBC
Reqs:
-lack of hydro nephro sis
-lack of extensive or multi focal TIS
-tumor size <6 cm
Kidney Cancer stage 1 (up to 7 cm)
T1a
-Partial nephrectomy (preferred) OR
-ablative techniques (<3 cm) OR
-active surveillance Or
-radical nephrectomy (select pts)
T1b
-partial nephrectomy OR
-radical nephrectomy OR
-active surveillance (select pts) OR
Kidney cancer stage II
-Partial nephrectomy OR
-radical nephrectomy
If grade 4 clear cell +/- sarcomatoid features- *adjuvant pembrolizumab x1 yr
Kidney cancer stage III
-radical nephrectomy OR
-partial nephrectomy (select pts)
—> adjuvant Pembrolizumab x1 yr or sunitinib is an option (not a good option) or surveillance
If non-clear cell: surveillance or clinical trial
Metastatic (stage IV) clear cell RCC (kidney)
Favorable/ good risk
Category 1 options:
-axitinib + Pembrolizumab
-cabozantinib (40 mg) + nivolumab
-lenvatinib + Pembrolizumab
*first assess for active surveillance or cytoreductive nephrectomy
-adjuvant pembro x 1yr following metastectomy within 1 yr of nephrectomy
Metastatic (stage IV) clear cell RCC (kidney)
Poor/intermediate risk
Category 1 options
-axitinib + pembrolizumab
-cabozantinib (40 mg) + nivolumab
-lenvatinib + pembrolizumab
-ipilimumab + nivolumab
Other:
Cabozantinib If can’t take ICI (60 mg daily)
*first assess for active surveillance or cytoreductive nephrectomy
-adjuvant pembro x1 yr following metastectomy within 1 yr of nephrectomy
Note: ICI + ICI has limited duration- opposed to TKI which is continued indefinitely
Non-clear cell RCC
(Likely not big exam question)
temsirolimus for poor prognosis (at least 3 risk fxs)*
otherwise:
-cabozantinib (preferred)
-clinical trial OR
-sunitinib OR
-papillary RCC- Cabozantinib is preferred TKI
-FH deficient RCC- bevacizumab + erlotinib
- Chromophobe RCC- bevacizumab/lenvatinib + everolimus
-renal medullary carcinoma and collecting duct carcinoma- platinum based chemo
-SDH deficient RCC- VegF TKI
Kidney cancer- who can be considered for active surveillance?
Favorable or intermediate risk, limited or no dx symptoms, favorable histologic profile, long interval b/w nephrectomy and development of Mets, limited burden of Mets
Kidney cancer- who can be considered for cytoreductive nephrectomy?
-Good PFS
-lung only Mets
-good prognosis risk
Metastatic (stage IV) kidney cancer
Second line
Preferred
-Cabozantinib (cat 1)
-nivolumab (cat 1)
-lenvatinib + everolimus
Other
-axitinib (cat 1)
-tivozanib (cat 1 if 2 prior regimens)
-belzutifan (if prior pd1 and vegf)
-all first line options
-Pazopanib
-sunitinib
-axitinib + avelumab (cat 3)
Metastatic (stage IV) kidney cancer with bone Mets
-bone directed RT
-bisphosphonate or rank-L
-cabozantinib containing regimen
Metastatic (stage IV) kidney cancer with brain Mets
-brain directed RT and/or surgery
Metastatic (stage IV) kidney cancer with sarcomatoid features
-ipilimumab + nivolumab has strongest evidence OR
-ICI + TKI
Prostate CA: all of the following
-cT1c
-grade group 1
-PSA<10
-<3 biopsy cores positive, <50% cancer in each
-PSA density <0.15ng/mL/g
Very low risk
Expected survival
<10y: observation
10-20y: active surveillance
>20y: active surveillance, RT, or RP (+/- EBRT +/- ADT)
Notice don’t use ADT alone unless very short life expectancy
Prostate CA:
-cT1-cT2a
-grade group 1
-PSA<10
Low risk
Expected survival
-<10y: observation
->10y: active surveillance, RT, RP (+/- EBRT +/- ADT)
Notice don’t use ADT alone unless very short life expectancy
Prostate CA:
-cT2b-cT2c
-grade group 2 or 3
-PSA 10-20
Intermediate risk
Life expectancy
<5y: observation
Favorable: 1 of above risk factors, grade group 1-2, <50% bx cores pos
-5-10y: observation, RT
->10y: active surveillance, RT, or RP +/- PLND (+/- EBRT +/- ADT)
Unfavorable: 2-3 of above factors, grade group 3, >50% bx cores pos
-5-10y: observation, EBRT + ADT, or EBRT + brachy +/- ADT
-10y: RP + PLND (+/- EBRT +/- ADT), or EBRT + ADT, or EBRT + brachy +/- ADT
Notice don’t use ADT alone unless very short life expectancy
Prostate CA: ONE of the following
-cT3a
-grade group 4 or 5
-PSA>20
High risk
Life expectancy
-<5 y and asymptomatic: observation or ADT or EBRT
->5 y or symptoms: EBRT + 1.5-3y ADT, or EBRT + brachy + 1-3y ADT (cat 1), or RP + PLND (+/- EBRT +/- ADT)
Notice don’t use ADT alone unless very short life expectancy
Prostate CA: at least one of the following
-cT3b-cT4
-primary Gleason pattern 5
-2-3 high risk features
->4 cores w grade group 4 or 5
Very High risk
Life expectancy
-<5 y and asymptomatic: observation or ADT or EBRT
->5 y or symptoms: EBRT + 1.5-3y ADT + abiraterone, or EBRT + brachy + 1-3y ADT (cat 1), or RP + PLND (+/- EBRT +/- ADT)
notice we’re not using second gen antiandrogens here
Prednisone is once daily with abiraterone in this setting
Prostate CA: any T, N1, M0
Regional
Life expectancy:
-<5y: observation or ADT
->5y: ADT + EBRT + abiraterone (preferred), or ADT + EBRT, or ADT +/- abiraterone, or RP + PLND (+- EBRT +- ADT)
Notice don’t use ADT alone unless very short life expectancy
Prednisone is once daily with abiraterone in this setting
Prostate CA: biochemical recurrence (rising PSA w/o metastatic dx)
m0CSPC
-if short PSA doubling time (<12 months) or long life expectancy: ADT or enzalutamide +/- ADT (PSADT <9 mo, psa >2 over nadir after RT or 1 after RP)
-if long PSA doubling time or short life expectancy: monitoring
Consider intermittent ADT
Prostate CA: m0CRPC
PSADT >10 months
Continue ADT
-monitoring (preferred)
-other secondary HT
Prostate CA: m0CRPC
PSADT <10 months
continue ADT
Preferred:
-novel (second gen) antiandrogens: (apalutamide, enzalutamide, darolutamide)
*note darolutamide ok here but for metastatic you need to give it with docetaxel
Other:
-secondary HT
-androgen withdrawal
-dex or pred
-ketoconazole (give w/ hydrocortisone)
Prostate CA: m1CSPC
-ADT + (abiraterone OR apalutamide OR enzalutamide)
-ADT + docetaxel + (abiraterone OR darolutamide)
*triplet therapy better if need faster response (high volume (viseceral mets or 4+ bone Mets with 1 outside vertebral column) or symptomatic from mets))
abiraterone only for de novo metastatic dx *in CS setting (can still add later)
docetaxel- in *castration sensitive dx only for de novo high volume dx
Notice we don’t use PARP inhibitors unless mCRPC- not used in m0 or mCSPC
Prostate CA: m1CRPC
(Essentially second line)
Prior ADT only (rare)
-docetaxel OR
-abiraterone OR
- enzalutamide
BRCA mutation
-Olaparib + abiraterone
-Niraparib + abiraterone
HRR mutation
-talazaparib + enzalutamide
Prostate CA: m1CRPC
(Essentially second line)
Prior ADT + novel HT
Docetaxel
BRCA mutation
-Niraparib + abiraterone
-Rucaparib (preferred)
HRR mutation
-Olaparib (preferred)
-talazoparib + Enzalutamide
Prostate CA: m1CRPC
(Essentially second line)
Prior ADT + docetaxel
Category 1
-abiraterone
-enzalutamide
Other:
Cabazitaxel
BRCA mutation
-Olaparib + abiraterone
-Niraparib + abiraterone
HRR mutation
-talazaparib + enzalutamide
Prostate CA: m1CRPC
(Essentially second line)
Prior ADT + docetaxel + novel HT
Category 1
-cabazitaxel
-Lu-177-PSMA-617 (if PSMA +)
Other:
-Docetaxel rechallenge (if no prior progression)
-mitoxantrone + prednisone (last line if no other options)
BRCA mutation
-Rucaparib
HRR mutation
-Olaparib
Prostate CA: m1CRPC
Regardless of prior therapy if pt has bone mets
Radium-223
If no visceral mets
Prostate CA: aggressive variant prostate CA
Cabazitaxel + Carboplatin
- add GCSF
Prostate CA: m1CRPC
-MSI-high, dMMR, or TMB>10
continue ADT
Pembrolizumab
Prostate CA: m1CRPC
BRCA mutation
this is mCRPC only
Olaparib- indicated after androgen receptor directed therapy (enzalutamide or abiraterone)- any HRR mutation (except PPP2R2A)
Rucaparib- indicated after androgen receptor directed therapy and taxane BRCA mutation only
Note: it might be better to use chemo first in eligible patients (not clear cut)
Prostate CA: m1CRPC
Any HRR mutation (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD54L
Olaparib- indicated after androgen directed therapy
Note: it might be better to use chemo first in eligible patients (not clear cut)
Prostate and breast CA: on AI(post menopausal) / LHRH/tamoxifen(premenopausal)/ADT, FRAX 10-y hip fx risk >3%, major osteoporosis related fx >20%
Above HT with T-score < -2 (breast)
-alendronate 70 mg weekly
-zolendronate 5 mg yearly or 4 mg q6 months
-denosumab 60 mg q6 month
Also calcium and vit D
Notice for prostate we need risk score, we don’t just tx, but for AI, tamoxifen or LHRH don’t need risk assessment score (I think, but in module still lists these tools as a way to determine who needs BMA in breast cancer)
Prostate CA CRPC: bone Mets
Bone protecting agent
-denosumab 120 mg q4wk (preferred)
+ calcium and vit D
-or zolendronate q3-4 wks or q3 mo (but denosumab is superior here)
This is for reductionis SRE in patients with bone Mets!!!
Not for CSPC EVEN IF PATIENT HAS BONE METS
When does PD-L1 expression matter/not matter in bladder cancer?
Can use atezolizumab first line in cisplatin ineligible patients- but this requires PD-L1 expression (>5%). Can use atezolizumab and pembro in platinum ineligible pts regardless of PD-L1.
Also doesn’t matter for second line I don’t think.
Double check this answer at some point
also atezolizumab no longer indicated for bladder cancer but still in NCCN guidelines
Outpatient tx of FN
Augmentin + cipro
Others:
-augmentin + levo
-moxifloxacin
Note: if pt was getting FQ ppx they will NOT be a candidate for PO abx
Febrile neutropenia ABX ppx
levofloxacin
Others:
-bactrim
-3rd gen CEPH
Germ cell tumor regimen details
BEP q21 days x 3
-bleomycin 30 mg IV weekly
-etoposide 100 mg/m2 d1-5
-cisplatin 20 mg/m2 d1-5
EP q21 days x 4
-etoposide 100 mg/m2 d1-5
-cisplatin 20 mg/m2 d1-5
*good risk, stage 2, or viable germ cell tumor at surgery following first line chemo
Other:
VIP q21 days- WITH G-CSF
-etoposide 75 mg/m2 d1-5
-ifosfamide 1200 mg/m2 d1-5 (w Mesna)
-cisplatin 20 mg/m2 d1-5
*for int or poor risk or for pts with viable germ cell tumor at surgery following first line chemo
Metastatic germ cell tumor- second line
(Relapse or as indicated following primary chemo)
Conventional dose
1. TIP q21 days x4- WITH G-CSF
-paclitaxel + ifosfamide + cisplatin
- VeIP q21 days x4- WITH G-CSF
-Vinblastine + ifosfamide + cisplatin
High dose chemo then ASCT
1. Carboplatin + etoposide
2. Paclitaxel + ifosfamide + Carboplatin + etoposide
Metastatic germ cell tumor- third line (high dose chemo not previously used)
- Carboplatin 700 mg/m2 + etoposide 750 mg/m2
- Paclitaxel + ifosfamide + Carboplatin + etoposide
These are myeloablative ASCT regimens
followed by ASCT
Metastatic germ cell tumor- third line (high dose chemo and ASCT previously used)
- Gemcitabine + paclitaxel + oxaliplatin
- Gemcitabine + Oxaliplatin
- Gemcitabine + paclitaxel
- Etoposide (oral)
this is more palliative
Germ cell tumor: Seminoma
Stage 1A/1B
-RIO —>surveillance (preferred)
-adjuvant RT
-Adjuvant carbo AUC 7 x1-2
Stage IS
-re-image
Stage IIA/IIB
-BEP x3, EP x4
-RT (non-bulky <3cm)
Stage IIC/III
RIO—> chemo
-good risk: BEP x3, EPx4
-int: BEP x4, VIP x4
Following chemo for IIC/III
-No or <3cm residual dx and normal tumor marker: surveillance
-Residual mass >3cm and normal markers—> PET scan >6 wks after chemo (unlike non-seminoma which does surgery)
-if positive: RPLND, TIP, VIP
-if complete resection of residual dx: EP, TIP, VIP, VeIP x2
-if incomplete resection of residual dx: full course second line
-if progression: second line or ASCT
DONT DOSE REDUCE CHEMO UNLESS ANC <500 or scr >1.5
Germ cell tumor: non-Seminoma
Stage 1
-Surveillance (preferred if no risk fx for relapse)
-nerve sparing RPLND
-BEP x1 (unless pure teratoma)
Stage IS
-EP x4, BEP x3
Stage IIA/IIB
-Normal post orchiectomy tumor markers:
-RPLND
-EP x4, BEP x3
-Elevated post orchiectomy tumor markers:
-EP x4, BEP x3
After stage IIA/IIB
-negative tumor markers and no residual dx or <1cm:
-surveillance
-RPLND (select pts)
-negative tumor markers and residual dx >1cm: nerve sparing RPLND
-after RPLND:
-N0: surveilllance
-N1-2: EP x2, BEP c2
-N3: EP x4, BEP x3
Stage IIC/ IIIA (good risk)
-EP x4, BEP x3
Stage IIIB (int risk)/ IIIC (poor risk)
-BEP x4, VIP x 4
-EP x4, BEP x3 ok if intermediate risk and LDH is the only reason
Risk for relapse: lymphovascular, spermatic cord, or scrotum invasion
********
After primary chemo
-CR and negative tumor markers: Surveillance or RPLND (unlike seminoma which does PET scan)-bc it’s usually teratoma so can’t do chemo
-PR, residual mass, normal tumor markers: EP, TIP, VIP, VeIP x2 (or surveillance if teratoma or necrosis)
-PR residual mass, abnormal tumor markers
-elevated and rising: second line
-elevated and stable: surveillance
-mildly elevated and normalizing:
-surgical resection
- surveillance if teratoma or necrosis
-other histology: EP, TIP, VIP, VeIP x2
DONT DOSE REDUCE CHEMO unless ANC <500 or scr>1.5
Chondrosarcoma
Primary therapy is surgery
-dasatinib
-Pazopanib
-ivosidenib (IDH1 mutation)
If unresectable, metastatic of de-differentiated- tx like osteosarcoma
If mesenchymal- tx like Ewings
Undifferentiated pleomorphic sarcoma of bone
Osteosarcoma like regimen for neoadjuvant and adjuvant chemo
*UPS
Dedifferentiated liposarcoma
Doxorubicin
Spermatocytic seminoma
Surgery (radical orchiectomy) only
*older men and rarely metabolize
Schwannoma treatment (benign)
Surgery only
Ovarian cancer surgical resection goal?
When can you do fertility preserving surgery?
Optimal cytoreduction: <1 cm residual dx
Suboptimal: > 1cm residual dx
*note: can do fertility sparing surgery for stage 1A and 1B
Ovarian Stage I
Stage 1A/1B low grade serous or grade 1-2 endometrioid
-Surgery alone -> observation
Stage 1A/1B high grade serous or grade 2-3 endometrioid, stage 1C
-Paclitaxel 175 mg/m2 + Carboplatin AUC 5-6 q3w
Others:
-Liposomal dox + Carboplatin
-docetaxel + carboplatin
Note
-3 cycles only for low grade, high grade serous gets 6 cycles
Ovarian: Stage II-IV
<70 years old
-Paclitaxel 175 mg/m2 + Carboplatin AUC 5-6
-Paclitaxel 175 mg/m2 + Carboplatin AUC 5-6 + bevacizumab + bevacizumab maintenance
>70 years old or comorbidities
-Paclitaxel 135 mg/m2 + Carboplatin AUC 5
-paclitaxel 60 mg/m2 + Carboplatin AUC 2 weekly (instead of every 3 weeks)
Other options (<70y)
-docetaxel + Carboplatin
-liposomal doxorubicin + Carboplatin
Notes:
-we still do surgery
-6 cycles of chemo (q21 days)
-for stage 3 HIPEC (hyperthermia IP chemo) w/ cisplatin 100 mg/m2 is and option at time of IDS
Ovarian: mucinous carcinoma
-5FU + leucovorin + Oxaliplatin (FOLFOX)
-capecitabine + Oxaliplatin (CAPOX)
-paclitaxel + Carboplatin
*can add bevacizumab for stages II-IV Is this supposed to be stage III-IV? NO!
Ovarian Cancer: IP chemo
Stage 2-3
-optimal cytoreduction (<1 cm)
-no bowel obstruction or bowel surgery
-good PFS
-normal renal function
-no pre-existing neuropathy
paclitaxel 135 mg/m2 IV —> cisplatin 75 mg/m2 IP—>paclitaxel 60 mg/m2 IP
-warm IP fluids, aggressive hydration (prevent renal function), aggressive antiemetics *(highly emetogenic regimen before day 2 cisplatin)
Note: paclitaxel is given over 3 hours NOT 24h and cisplatin is 75 mg not 100 mg
When do we do neoadjuvant instead of adjuvant chemo for ovarian cancer?
Bulky stage 3-4 unlikely to be optimally cytoreduced (<1 cm with surgery) and/or poor surgical candidate
Assess for interval debunking surgery after 3 cycles (3 cycles—> surgery—> 3 more cycles…could technically do all 6 then surgery then more chemo)
Same regimens except no IP. And hold bevacizumab cycle before and after surgery
Ovarian CA maintenance (primary)
How long is it continued?
Note: HRD+ means homologous recombinant DEFICIENT (ya little dumbass)
Notice the word ”REGARDLESS doesn’t mean “wild type”
Bevacizumab:
-regardless of HRD and BRCA wildtype
-must have used in upfront regimen
Bevacizumab + Olaparib
-PR/CR to 1st line chemo
-Germline/somatic BRCA mutation when bevacizumab used in upfront (cat 1) OR
-BRCA wild type but HRD+ (mychoice CDx score 42+) when used upfront
Olaparib
-PR/CR to 1st line chemo
-germline/somatic BRCA mutation
Niraparib (preferred over Rucaparib bc has fda and NCCN approval)
-PR/CR to 1st line chemo
-regardless of BRCA or HRD
-unless BRCA wildtype and Bev was used- use Bev maintenance
Rucaparib
-PR/CR to 1st line chemo
-Regardless of BRCA or HRD
-unless BRCA wildtype and Bev was used- use Bev maintenance
Usually continue for 2 years, dx progression, or unacceptable toxicity. Except Niraparib: 36 months and bevacizumab: 15 months
”stable disease” is not CR/PR and does not qualify for PARP maintenance
Recurrent ovarian CA: platinum sensitive (platinum free interval >6 months)
-carbo + gemzar +/- bevacizumab
-carbo + paclitaxel +/- bevacizumab
-carbo + Liposomal dox +/- bevaciz
-cisplatin + gemcitabine
Targeted therapy:
-bevacizumab
Note: don’t retreat for biochemical recurrence (CA-125), wait for measurable or symptomatic disease
Recurrent ovarian CA: platinum resistant (platinum free interval <6 months)
-docetaxel
-oral etoposide
-Gemcitabine
-liposomal dox +/- bevacizumab
-paclitaxel (weekly) +/- bevacizumab
-topotecan +/- bevacizumab
-oral cyclophosphamide + bevacizuma
Targeted:
Bevacizumab
Other:
-Mirvetuximab (FRa positive- >75%)
-pembro: msi-h, dMMR, TMB-h and no satisfactory alternatives
Note: don’t retreat for biochemical recurrence (CA-125), wait for measurable or symptomatic disease
Recurrent Ovarian maintenance platinum sensitive (platinum free interval >6 months)
no PARP inhibitors for platinum resistant recurrence
Olaparib:
-PR/CR to 2+ line therapy
-regardless of BRCA
Rucaparib:
-PR/CR to 2+ line therapy
-must have BRCA mutation
Niraparib:
-PR/CR to 2+ line therapy
-must have germline BRCA mutation
-if starting at a reduced dose, may increase back if no worsening thrombocytopenia
bevacizumab:
-PR/CR to 2+ line therapy
-if used in therapy for recurrent dx
*continue until dx progression or unacceptable toxicity
Recurrent ovarian CA: with specific gene mutations
BRFA V600E: Dabrafenib + trametinib
NTRK: entrectinib, larotrectinib
RET: Selpercatinib
MSI-H, dMMR, TMB-H: pembro (only
If no other treatment options left)
TMB-H: dostarlimab for recurrent
Cervical cancer
(Small cell NECC)
Stage I-IIA
-Surgery + RT
Stage IIB-IVA, recurrent, metastatic
RT most important:
Chemo radiation:
-cisplatin + etoposide + RT
(Can use carbo is cis intolerant)
Endometrial (uterine) cancer stage I-II
Pretty much just surgery (TH/BSO) followed by observation or RT (pelvic EBRT and/or vaginal brachytherapy NOT whole pelvic RT)
Note: bx proven grade I endometrioid limited to endometrium can skip surgery for fertility sparing and just do HT (continuous progesterone therapy with megestrol, medroxyprogesterone, or levonorgestrel IUD)
Could consider systemic therapy for stage II or IB (grade 3)
For high risk (serous carcinoma, clear cell carcinoma, undifferentiated/Dedifferentiated carcinoma, carcinosarcoma) use systemic therapy much earlier- stage 1, more like ovarian
Note: early stage endometrial is the most curable gyn CA
Endometrial (uterine) cancer stage III-IV
Surgery—>chemo—> +/- RT
Chemo: Carboplatin + paclitaxel + pembro/dostarlimab (regardless of MMR) OR + trastuzumab (HER-2+ uterine serous or carcinosarcoma)
Chemo-Radiation
-cisplatin + RT—> carbo + paclitaxel
Endocrine therapy:
(For ER/PR+, low grade endometrial only- use instead of chemo)
-tamoxifen, AI, fulvestrant, progestin products
Notice we don’t start chemo
Until stage III- unlike ovarian (stage 1) and cervical (stage IIB)
Endometrial (uterine) cancer: recurrent
Local recurrence
Surgery and/or RT-pelvic EBRT + brachytherapy (Look at what was previously given)
Distant recurrence
Chemo:
Carboplatin + paclitaxel +/- pembro/dostarlimab (regardless of MMR) + trastuzumab (if HER-2+ uterine *serous or carcinosarcoma)
Endocrine therapy:
(For ER/PR+, low grade endometrial only- use instead of chemo)
-tamoxifen, AI, fulvestrant, progestin products
Other:
-lenvatinib + pembro (NOT MSI-H or dMMR) (Category 1)
-pembro, nivo, dostarlimab, avelumab alone (MSI-H /dMMR or TMB-H)
-single agents therapy: cis, carbo, dox, paclitaxel
Endometrial CA: hormone therapy for metastatic or recurrent
Recurrent or metastatic
-Megestrol/ tamoxifen alternating
-everolimus + letrozole
Uterine limited dx and fertility sparing
-levonorgestrel IUD
ER/PR+, low grade endometrioid, instead of chemo
Pediatric ALL inductions standard risk
-dex + vincristine + calaspargase
Note: dex in 10+ y/o increases fungal infxns and osteonecrosis
Pediatrics ALL induction high risk
-steroid (dex <10, pred 10+), vincristine, calaspargase, anthracycline
Note: dex in 10+ y/o increases fungal infxns and osteonecrosis
ALL induction CNS directed therapy
Diagnostic LP with IT Cytarabine given on or before induction LP
Then intermittent IT chemo
need plt >/= 100k
Cytarabine d.o.c bc active in ALL and AML
Pegaspargase vs calaspargase
Peg: >21 y/o
Cal: </= 21 y/o
Pediatrics ALL maintenance
Standard backbone:
-daily mercaptopurine (6MP) PO + weekly PO MTX+ intermittent pulses of vincristine + corticosteroid
-increase (if sustained >6-8 weeks) 6MP and MTX doses by 25% to maintain ANC 500-1500
-if ANC <500, hold both until recovery and restart at lower dosing
TPMT dose adjustments for thiopurines
Homozygous wild type (normal metabolizer- 1/1): normal dose
Heterozygous (intermediate- 1/2, 3A, 3B, 3C, or 4): 30-80% of normal dose
Homozygous deficient (poor- *2/3A, 3C/4): 10% full dose (3 times per week per lecture but not NCCN)
*if int for both NUDT15 and TPMT give further dose adjustment
NUDT15 dose adjustments for thiopurines
Homozygous wildtype (normal metabolizer- 1/1): normal dose
Heterozygous (intermediate- 1/2, *3, or 9):
-6MP: 30-80% *of full dose
Homozygous deficient (poor- 2/3):
-6MP: 10 mg/m2/day
-6TG: 25% dosing
*if int for both NUDT15 and TPMT give further dose adjustment
Pediatric Non-Hodgkin’s lymphoma (Burkitts) group A low risk
COPAD x2
(Cyclophosphamide, vincristine, prednisone, doxorubicin)
no IT or HD-MTX needed
no reduction or consolidation like group B/C and no maintenance like group C
Pediatric Non-Hodgkin’s lymphoma (Burkitts) group B intermediate risk
-COP x1 (cyclophosphamide + vincristine + prednisone)-REDUCTION
-COPADM x2 (cyclophosphamide + vincristine + prednisone + doxorubicin + HD-MTX)-INDUCTION
-CYM x2 (Cytarabine + HD-MTX)-CONSOLIDATION
No maintenance like group C
Pediatric Non-Hodgkin’s lymphoma (Burkitts) group C high risk
-COP x1 (cyclophosphamide + vincristine + prednisone)-REDUCTION
-COPADM x2 (cyclophosphamide + vincristine +prednisone + doxorubicin + HD-MTX)-INDUCTION
-CYVE x2 (HD-Cytarabine + etoposide)-CONSOLIDATION
Maintenance x2-4 cycles
Pediatric medulloblastoma
Average Risk
-surgery + reduced dose RT + weekly vincristine —> chemo x8
Chemo is:
-cisplatin + vincristine + cyclophos OR
-cisplatin + vincristine + lomustine
High Risk
3+ y/o: surgery + standard dose RT + weekly vincristine —> chemo (VCP x8 (vincristine + lomustine + prednisone)
<3 y/o: surgery + chemo +/- HCT (avoid RT in <3y)
Give RT within 4 weeks post surgery
Pediatric Neuroblastoma: high risk
Induction: surgery + RT
Chemo= CAV cycle 1,2,4,6 (cyclophos , dox, vinc) and cis + etop cycle 3 and 5
Consolidation: myeloablative chemo + tandem autologous stem cell transplant
Maintenance: isotretinoin +/-Dinutuximab
___________________________________
Note: low risk (stage 1-2) dx is tx with surgery alone
GM-CSF: potentials antibody dependent cell mediated toxicity
Hyperdiploid is favorable risk
Wilms tumor tx
-surgery is mainstay
-RT for stage III or greater
-chemo
-low risk (Stage II) EE-4A (dactinomycin + vinc)
-standard-high risk (stage III+): DD-4A (dactinomycin + vinc + dox)
-sometimes add cyclophos for higher risk
*this is a type of kidney cancer- almost always in children
LOH at chromosomes 1p and 16q is poor prognostic fx- seen in standard and high risk
Bladder gem-cis vs dd-MVAC
-ddMVAC preferred in neoadjuvant setting, either in metastatic setting
Atezolizumab for bladder cancer update
Indications withdrawn!! Still in NCCN guidelines
When to use neoadjuvant chemo in sarcomas (as opposed to adjuvant)
Large tumors (>10cm) or high grade
Cervical cancer (squamous cell, adenocarcinoma, adenosquamous carcinoma)
Stage I-IIA
-Surgery + RT
Stage IIB-IVA
Chemo radiation:
-cisplatin + RT (EBRT + brachy)
(carbo if cisplatin intolerant)
-cisplatin dose is 40 mg/m2 q7d x5-6 weeks
-may cap dose at 70 mg
Notice IVA NOT IVB
If chemo alone
-cisplatin + paclitaxel +/- bevacizumab +/- pembro (PD-L1 pos)
Cervical cancer (squamous cell, adenocarcinoma, adenosquamous carcinoma) persistent, recurrent, or metastatic; stage IVB
-Cisplatin (or carbo) + paclitaxel +/- bevacizumab + pembrolizumab (if PD-L1 positive: (CPS 1+)- q3wk
-paclitaxel + topotecan + bevacizumab
If above fails
-Tisotumab-vedotin
-pembro (cps 1+, MSI-H/TMB-H)
-cemiplimab
-paclitaxel
-fam-trastuzumab deruxtecan (HER-2+)
Notice IVB NOT IVA
Chemo pediatric astrocytoma or brain stem Tumors
High grade gliomas
Astrocytomas/brain stem
-Carboplatin + vincristine OR
-thioguanine + Procarbazine + lomustine + vincristine
-surgery is primary- reserve chemo for symptomatic, progressive, or recurrent dx
-RT often avoided if possible
High grade gliomas
-3+: RT + TMZ —> Adjuvant TMZ + lomustine
-<3:
-cyclophos + vinc + cis + etop
-vinc + carbo + TMZ
Pediatric burkitts lymphoma -reduction phase
-Low dose cyclophos + vincristine + pred
-goal to decrease by 20% to reduce TLS risk
Systemic therapy for pediatric retinoblastoma
Intraocular
ICIR group A: focal therapy only
ICIR group B: systemic VC: vinc + Carbo x8 (and focal)
ICIR group C-D: systemic VEC- vinc + etop+ Carbo x6 (and focal)
ICIR group E: enucleation
-note: intra-arterial chemo is an option here (unlike extraocular)
Extraocular
-Orbital/locoregional: enucleation, systemic chemo, EBRT
-metastatic: systemic chemo, maybe enucleation and EBRT, maybe ASCT
-Consider intra-arterial chemo (carbo, Melphalan, or topotecan )
-for group E and extraocular dx you will need systemic chemo and likely enucleation
-focal therapy: photocoagulation, cryotherapy
-highly radiosensitive: consider EBRT
Metastatic (rare)
-induction chemo (cyclo, cisplatin, vincristine, etoposide)—> consolidation with HD chemo and ASCT
Early stage breast cancer: HR+, HER-2 negative, post menopausal
-T< 0.5 cm and N0: ET or observation
-T >0.5 cm or LN+:
-PS<26: ET
-PS 26+: ET + chemo
-LN 4+ (N2/N3): ET + chemo
Early stage breast cancer: HR+, HER-2 negative, pre-menopausal, LN (-)
-T<0.5 cm: ET or observation
-T>0.5 cm:
-PS 16+: ET + chemo
-PS <16: ET
Notice: is premenopausal women there is the exception and you can use OncotypeDx in LN negative rather than 1-3 LN like post menopausal m
Early stage breast cancer: HR+, HER-2 negative, pre-menopausal, LN (+)
ET + chemo
Early stage breast cancer: HR +, HER-2+, LN (-)
ET + chemo + trastuzumab (if chemo given)
could be less aggressive if small tumor (<0.5 cm) but chemo still and option
Early stage breast cancer: HR +, HER-2+, LN (+)
ET + chemo + trastuzumab and Pertuzumab
Early stage breast cancer: HR (-), LN (-)
-HER-2 (+):chemo + trastuzumab
-HER-2 (-):chemo (nothing if LN (-) AND T<0.5cm)
can be less aggressive for smaller tumors (usually <0.5cm) chemo is still an option if HER-2+
Early stage breast cancer: TNBC, LN (-) and LN +
LN +: Chemo
**</=0.5cm AND LN (-): no adjuvant therapy **
Early stage breast cancer: HR (-), HER-2+, LN (+)
Chemo + trastuzumab and pertuzumab
Early stage breast cancer: pre-menopausal, endocrine therapy
Tamoxifen +/- OAS x5 years, THEN
-still premenopause: tamoxifen x5 more years
-post-menopause: 5 more years with AI
OAS for higher risk recurrence (young age, high grade tumor, LN involvement)- *unlike metastatic in which premenopausal women always get OAS with hormone therapy
Note: don’t confuse with BC prevention which has a duration of 5 years total
Notice we don’t differentiate b/w HER-2+ vs HER-2 negative like in the metastatic setting (although HER-2+ will also get HER-2 therapy IF CHEMO IS ALSO GIVEN)***
Tamoxifen preferred in men
Early stage breast cancer: post-menopausal, endocrine therapy
AI x5 years—> consider continuing for total of 7.5-10y (10 years for LN+)
Note: don’t confuse with BC prevention which has a duration of 5 years total
Notice we don’t differentiate b/w HER-2+ vs HER-2 negative like in the metastatic setting (although HER-2+ will also get HER-2 therapy-IF CHEMO IS GIVEN)
When is abemaciclib added to ET for early stage BC?
HR+, HER-2 (-), LN (+):
-ki-67 20%+
-4+ LN
-1-3 LN + (grade 3, OR T= 5+ cm (T3), OR ki67 20%+
What are the preferred chemo regimens for early stage HER-2 (-) breast cancer?
-dose dense (q2week) Dox + cyclo—-> paclitaxel (weekly) (maybe better if grade 3 or LN 4+)- 4 cycles of each
-docetaxel + cyclophosphamide (TC)- if can’t take anthracycline
STAGE II-III TNBC: (for stage I TNBC need to use above regimens):
NEOADJUVANT not adjuvant
taxane (paclitaxel) + Carboplatin +/- pembrolizumab x4 followed by AC (cyclo + dox/epirubicin) + pembro x4 follow by more pembro in adjuvant setting x9 (only pembro alone is adjuvant)
Who gets neoadjuvant chemo in breast cancer?
Which regimens are used?
early stage
-inflammatory BC
-dx likely to be converted to respectable after chemo
-reduce extent of surgery
-preferable to delay surgery
-TNBC: LN+, or at least T1c
-HER-2+: LN + or high risk LN (-)
-pre-menopausal LN+ (fellow on call)
stage IIIa or higher (locally advanced) will probably get it? YES!
-same regimens as adjuvant unless TNBC MAY use taxane + Carboplatin +/- pembro
-AC—>T may be better than TC if LN positive
-can use pembro with chemo neoadjuvant in TNBC- (and give more pembro adjuvantly)
Can do ET for postmenopausal women
TNBC: residual dx after neoadjuvant chemo
Capecitabine- start after RT
-if no residual dx just observation of pembro x9 cycles (only if given neoadjuvant already)
TNBC: neoadjuvant and adjuvant
Neoadjuvant: chemo (carbo + taxane) + pembro
Adjuvant: pembro
*pd-l1 expression not required here (it is required in metastatic setting)
Early stage breast cancer HER-2+ chemo regimens
-Trastuzumab + paclitaxel (T1, N0, LN-)
-THC (docetaxel + carbo + trastuzumab)
-TCHP (docetaxel + carbo + trastuzumab + pertuzumab)
*pertuzumab if T>2cm or LN+- double check the 2 cm
Early stage breast cancer HER-2+ chemo regimens
Trastuzumab + paclitaxel (T1, N0, LN-)
-THC (docetaxel + carbo + trastuzumab)
-TCHP (docetaxel + carbo + trastuzumab + pertuzumab)
*pertuzumab if T>2cm or LN+
Early stage breast cancer HER2+: residual dx after neoadjuvant therapy
-if no residual dx or no neoadjuvant treatment: complete 1 year of trastuzumab +/- pertuzumab
-if residual dx: ado-trastuzumab emtansine x14 cycles
Early stage breast cancer: HR+/ HER-2 +: extended adjuvant therapy
Neratinib x1 year after trastuzumab in pts with high risk recurrence (usually means LN+ and HR+ and HER2+)
Adjuvant bisphosphonates for TREATMENT of early stage breast cancer
For Risk reduction of distant Mets in POST-MENOPAUSAL with LN+ or high risk LN(-) (irrespective of HR or HER-2)
-Zolendronate 4 mg IV q6months x3 y or q3months x2 y
-or clodronate or ibandronate
note this is for risk reduction of mets in patients with EARLY STAGE BC……..DONT CONFUSE WITH REDUCTION OF SRE IN PATIENTS WHO ALREADY HAVE BONE METS
Menopause can be natural or induced (LHRH agonists)
Not for men, not for premenopausal, don’t use denosumab
Metastatic breast cancer: extensive or symptomatic visceral involvement
HER-2+: chemo + anti-her2 therapy
HER-2(-): chemo (+ pembrolizumab if TNBC and pd-l1 cps >10% or PARP if appropriate
*olaparib or talazoparib if germline BRCA
notice we’re not doing ET even if HR+ (can add on after chemo when appropriate)
Metastatic breast cancer: NO extensive or symptomatic visceral involvement
HER-2+: chemo + anti-her-2 (could do ET instead of chemo if HR+)
HER-2(-):
-HR+: ET
-HR(-): chemo + pembro (if pd-l1>10%)
*olaparib or talazoparib if germline BRCA
*basically the same is last notecard expect you can get away with ET instead of chemo for HR+/HER-2(-)
Metastatic breast cancer: endocrine therapy for HR+/HER-2(-)
-CDK 4/6-I (ribociclib preferred) + AI
-CDk 4/6-I (ribociclib or abemeciclib preferred) + fulvestrant
Second line*
-CDk 4/6-I (ribociclib or abemeciclib preferred) + fulvestrant
-alpelisib + fulvestrant (PIK3CA)
-capivasertib + fulvestrant (PIK3CA or AKT1/PTEN)
OAS required if premenopausal
Duration: continue until dx progression (unlike early stage)
Treat men the same as women here
Metastatic breast cancer: when is elacestrant indicated?
-ER+/HER-2(-), ESR1 mutated - progression following 1 or more lines of ET
-post-menopause
-given alone
When is alpelisb indicated in breast cancer?
-Metastatic breast cancer HR+/HER-2(-) with PIK3CA mutation after progression on ET
-post-menopause or premenopausal with OAS
-given with fulvestrant
Metastatic breast cancer: HR+/HER-2(-) with visceral crisis (severe organ dysfunction) or endocrine refractory
First line: chemo or PARP-I (if BRCA)
Second line:
-fam-trastuzumab deruxtecan (if HER-2 low)
-chemo or sacituzumab govitecan (if HER-2(-)
-Notice no PARP-I in second line like with TNBC)
Metastatic breast cancer systemic therapy options: TNBC
First line:
-chemo + pembro (cps>10%)
-chemo
-PARP-I (germline BRCA) or platinum-unlike HR+/HER-2 neg (germline BRCA)
Second line:
-PARP-I (germline BRCA) (unlike HR+/HER-2(-)) NOT PLATINUM LIKE IN FIRST LINE
-fam-traztuzumab deruxtecan (HER-2 low)
-chemo
-sacituzumab govitecan
Chemo options with pembro:
-paclitaxel or nab-paclitaxel
-Gemcitabine + Carboplatin
Metastatic breast cancer preferred chemo options (HER-2(-))
single agent:
Use one of these first:
-doxorubicin
-liposomal doxorubicin
-paclitaxel
Failed taxane and anthracycline
-capecitabine
-Eribulin
other
-Gemcitabine
-Vinorelbine
TNBC w/ BRCA mutation
-platinum (no taxane here like with early stage) (first line only)
Trick: In metastatic setting: HER-2+ drop the platinum, TNBC drop the taxane
Chemo options with pembro for TNBC
-paclitaxel or nab-paclitaxel
-Gemcitabine + Carboplatin
Metastatic breast cancer HR+/HER-2(+) endocrine therapy
Notice AI is ok for premenopausal -especially if progressed while on tamoxifen
-AI +/- trastuzumab
-AI +/- lapatinib
-AI +/- lapatinib + trastuzumab
-fulvestrant +/- trastuzumab
-tamoxifen +/- trastuzumab
*pre or post menopause
OAS required if premenopausal
use fulvestrant or steroidal AI if not sensitive to AI (less than a year since use)
non-steroidal AI
Note: if progressing on these you can do things like: change to steroidal AI, SERD, elacestrant, alpelesib, capivasertib (these 3 are actually HER-2 neg, but you get the idea) etc. After this we go to PARP-we only go to chemo when we have visceral crisis or after all these ET agents and PARP if applicable
Duration: continue until dx progression (unlike early stage)
Metastatic breast cancer preferred chemo options (HER-2+)
First line:
-THP: pertuzumab + trastuzumab + taxane (docetaxel preferred)
Second line:
-fam-trastuzumab deruxtecan
Third line:
-tucatinib + trastuzumab + capecitabine (especially if Brain Mets- after 1 prior line)
-ado-trastuzumab emtansine
Fourth line:
-margetuximab?
notice we give both traztuzumab and Pertuzumab for metastatic
Trick: In metastatic setting: HER-2+ drop the platinum, TNBC drop the taxane
Note: don’t switch therapy d/t presence of brain Mets if systemic dx is stable
Breast cancer bone modifying agents i patients with bone mets
-pamidronate 90 mg over 2 hours iv q3-4 wk
-zolendronate 4 mg iv q3-4 or q12 wks
-denosumab 120 mg iv q4 weeks
When to use BMA to prevent bone loss in breast/ prostate cancer pts?
DXA -1.5 to -2 consider it and definitely for -2+ or FRAX 10y major fx risk >20% or hip fx >3%
HT or ADT
Use osteoporosis dosing
Endometrial cancer adjuvant therapy sequencing
Give chemo first, then RT
*notice that chemo is adjuvant not neoadjuvant
Osteosarcoma chemo: adjuvant or neoadjuvant
Definitely neoadjuvant (category 1), but also can give adjuvantly
*Ewings also gets neoadjuvant
Role of neoadjuvant vs adjuvant chemo in soft tissue sarcoma
Neoadjuvant reserved for clinical trials, or highly select pts to avoid more aggressive surgery or amputation
Adjuvant- no proven role but DECREASES RECURRENCE
GIST: Adjuvant v neoadjuvant imatinib
-No definitive role for neoadjuvant: consider if surgical morbidity can be reduced by giving it
-Usually it’s just adjuvant
Which type of sarcomas are NTRKs good for?
GISTS
Sequencing in early stage BC
- Neoadjuvant chemo (if applicable) + HER-2
- Surgery
- Adjuvant chemo + HER-2
- RT and ET +/- abemeciclib (2y)
- Then PARP-I at least 2 weeks after RT
- Neratinib x1y following trastuzumab x1y
Note: RT given after chemo to avoid radiation recall
Start chemo within 30 days of surgery
Note: neoadjuvant HT is an option for post-menopausal HR+/HER-2(-)
m1CRPC MSI-H, dMMR, or TMB 10+
Pembrolizumab
Breast cancer prevention meds for high risk
When to use raloxifene?
Pre menopause: Tamoxifen 20 mg daily- 5 years
Post menopause: tamoxifen, Raloxifene (SERM), AI. -5 years
raloxifene is better than AI in postmenopausal women if low BMD and better than tamoxifen if pt has intact uterus
5 YEAR DURATION!!!
Dont confuse with HT therapy for tx of early stage BC which is often 10 years
Tx of hot flashes is breast cancer
-antidepressants (venlafaxine preferred)
-gabapentin (preferred)
-pregabalin
-clonidine
-oxybutynin
Low risk MDS: epo lvl<500
Epogen
*don’t give if epo lvl>500
Dose is 300 units/kg three times a week
do before luspatercept
Low risk MDS: ring sideroblast
Luspatercept
15%+ ring sideroblasts or 5%+ with SF3B1 mutation
Low risk MDS: del(5q) especially if this is the sole abnormality
Lenalidomide
can use Lenalidomide in non-del(5q) after using (or ruling out) luspatercept and epo, but before moving on the HMAs
Dont use if ch 7 abnormality
Low risk Hypoplastic MDS (blasts <5%)
Immunosuppression: ATG, cyclosporin, corticosteroids, eltrombopag (various combinations), ATGAM
Low risk MDS: failed prior therapies
HMAs: azacitadine, decitabine
use Lenalidomide even in non-del(5q) pts before moving on the HMAs
Failure: significant thrombocytopenia, or neutropenia or increased marrow blasts
High risk MDS: not a candidate for HCT
HMA:
azacitadine (preferred), or decitabine
High risk MDS: good PFS and few comorbidities
Allogeneic HCT (only cure for MDS)
-Can bridge with HMA
-can do high intensity chemo with AML regimen before HCT (poor response rate if complex karyotype or del(7q)
R/R:
-Ivosidenib
AML induction: young/ fit, or older than 60 but fit
(7 (Cytarabine) + 3 (Idarubicin 12 mg/m2/d or daunorubicin))
-If FLT3-ITD mutation: add midostaurin or quizartinib
-If FLT-TKD mutation: add midostaurin
-if core binding fx (inv(16), t(16;16), t(8;21) (don’t need CD33+): add Gemtuzumab ozagamicin
Daunorubicin dose is 60-90mg/m2/day x 3 days, 60 if combo with Gemtuzumab or midostaurin or quizartinib- wolverheme like dauno 90 in FLT-3 pts
Cytarabine dose is 100 mg/m2- don’t confuse with HIDAC
Notice IDH inhibitors are not used here
Note: AML induction is 28 days
Note: goal is blast <5% “hypoplasia”
Secondary AML induction
CPX-351 (Liposomal Daunorubicin and Cytarabine)
Note: AML induction is 28 days
AML: older and relatively fit
(60+ and declines or unfit for intensive therapy)
Preffered (more middle road)
-S.O.C: HMA (Aza cat 1) + venetoclax (could ignore FLT3 in this case)- middle of the road regimen
-HMA (aza cat 1) + Ivosidenib (If IDH-1 mutation)
Other (less intense than above)
-Ivosidenib (IDH-1 mutation)
-enasidenib (IDH-2 mutation)
-Gemtuzumab (CD33+)
-Glasdegib + LDAC
-venetoclax + LDAC
-LDAC
-HMA
-HMA + FLT3-I (probably not-see below)
unlike with young/fit pts, don’t act on FLT3 mutations
Notice IDH inhibitors are only used in older pts unfit for intensive therapy
continue therapies on indefinitely (unlike fit induction)
AML consolidation
Favorable Risk
-High dose Cytarabine (2-4 cycles)
-OR carry forward whatever was used initially
-can follow with allo HCT- BUT DONT GENERALLY NEED THIS FOR CURE!
Poor risk or consider for intermediate risk
-Allogeneic HCT (also give if CR2-takes 2 rounds of induction chemo)
Start consolidation within 2 weeks of hematologic recovery AND bone marrow showing CR
Bone marrow at day 14 to see that blasts <5%, then upon recovery (ANC >1000, plt>100k) repeat marrow to confirm still at blast <5%, then you can do consolidation- if refractory may need salvage
AML maintenance
Consider oral azacitadine in int/poor risk cytogenetics in pts who previously got intensive induction chemo and can’t go on to allo HCT for consolidation. >55y/o
Begin while pt is in CR:
-ANC >1000
-plt >100
-transfusion independent
-marrow blasts <5%
-no extramedullary dx
Relapsed/ refractory AML
-allo HCT if eligible (only cure for R/R)
-look for targetable mutations
Re-induction (often if relapse more than 1 yr, or before HCT)
-salvage chemo (hiDAC based: FLAG +/-IDA, MEC (mitoxantrone based), G-CLAC, CLA(+/-M) AKA CLAG (these are all HD-Cytarabine regimens with (mitoxantrrone/clofarabine/cladrabine/Fludarabine)
-5+2
-can repeat same regimen if remission >12 months
Low intensity for salvage
-Gemtuzumab (CD33+)
-gilteritinib (if FLT3-ITD or TKD mutation)
-Ivosidenib or olutasidenib (IDH-1)
-enasidenib (IDH-2)
Low intensity (used in practice but not great data)
-HMA +/- venetoclax
-LDAC +/- venetoclax
Note: refractory is pts who either don’t respond of relapse within 6 months
APL: low/int risk
notice risk difference compared to RCC and testicular and AML
Use Differentiating agents:
-all-trans-retinoids acid (ATRA) +arsenic trioxide
Maintenance: observation or ATRA + arsenic x1-2y
chemo free
Dont add a FLT-3-I even if FLT-3 mutation- don’t get tripped up
-PLT transfusion to goal fibrinogen of 30-50
-cryoprecipitate to goal of 100-150
APL: high risk
notice risk difference compared to RCC and testicular and AML
Use differentiating agent AND chemo:
Induction and consolidation:
-ATRA +/- arsenic + Idarubicin or Gemtuzumab ozogamicin
-consider IT therapy
Maintenance:
-ATRA + MTX + 6MP for 1-2y
Note: NCCN recommends differentiation syndrome ppx w/ pred 0.5 mg/kg/d or dex 10 mg q12 is high risk pts WBC>10
Dont add a FLT-3-I even if FLT-3 mutation- don’t get tripped up
-PLT transfusion to goal of 30-50
-cryoprecipitate to goal fibrinogen of 100-150
Treatment of differentiation syndrome
Dex 10 mg IV q12h x3-5d followed by 14 day taper
-continue differentiating agents if mild, hold if really bad (cardio respiratory)- except hold right away for olutasidenib
-causes by ATRA, arsenic, IDH-I, FLT3-I (AML drugs!)
all blasts mature into granulocytes at once and there’s a ton of cytokines and inflammatory processes. Lots of edema happens ~10-12days after first dose
(Dyspnea, peripheral and pulmonary edema, unexplained fever, hypotension, AKI)
Relapsed ALL
-Inotuzumab ozogamicin +/- TKI
-blinatumomab ozogamicin +/- TKI
-tisagenlecleucel (less 26 y/o)
-brexucabtagene autoleucel
-allogenic HCT if you can achieve CR
Bladder preservation chemo regimens (patients not getting cystectomy
-5FU + mitomycin
-cisplatin alone
-low dose Gemcitabine
Others:
-cisplatin + 5FU
-cisplatin + paclitaxel
For MIBC- given with RT after TURBT for bladder preservation
Reqs:
-lack of hydro nephro sis
-lack of extensive or multi focal TIS
-tumor size <6 cm
ALL (Ph negative) frontline ages 15-39
-CALGB 10403-Daunorubicin + vincristine + pred + pegAsparginase
-DFCI protocol 00-01-doxorubicin + vincristine + pred + HD-MTX + pegAsparginase
T-cell:
-COG AALL0434
ALL (Ph negative) frontline ages <65 without substantial comorbidities
WTF HAPPENED TO THIS CARD! It’s supposed to be ECOG1910!!
Low intensity:
-vinc + steroids
-POMP
Moderate:
-GMALL
-GRAALL
-EWALL
-PETHEMA ALLOLD07
-modified DFCI 91-01
-mini-hyper-CVD + Inotuzumab
High:
-hyper-CVAD (dose reduced Cytarabine)
-CALGB 9111
-ECOG1910
ALL (Ph negative) frontline ages >65
Low intensity:
-vinc + steroids
-POMP
Moderate:
-GMALL
-GRAALL
-EWALL
-PETHEMA ALLOLD07
-modified DFCI 91-01
-mini-hyper-CVD + Inotuzumab
High:
-hyper-CVAD (dose reduced Cytarabine)
-CALGB 9111
ALL (Ph positive) frontline ages 15-39
-EsPhALL: TKI + (cyclo + vinc + dauno + dex + Cytarabine + MTX + peg + pred)
-TKI + hyper-CVAD
-TKI + steroid
-TKI + vincristine + dex
-CALGB 10701 (TKI + dex + vinc + dauno + etop + MTX + Cytarabine)
-blinatumomab + TKI
Note: Same as adult <65 except EsPhALL is an additional option here
ALL (Ph positive) frontline ages <65 without substantial comorbidities
-TKI + hyper-CVAD alternating with HD-MTX and Cytarabine
-TKI + steroid
-TKI + vinc + dex
-CALBG 10701 (TKI + dex + vinc + dauno + MTX + etop + Cytarabine)
-blinatumomab +/- TKI
Note: Same as AYA except no EsPhALL
ALL (Ph positive) frontline ages >65
Low intensity:
-TKI + steroids
-TKI + vinc + dex
Moderate:
-EWALL (TKI + mx agent chemo)
-CALGB 10701 (TKI + mx agent chemo)
High:
-TKI + hyper-CVAD (dose reduced Cytarabine)
-Blinatumomab +/- TKI
pretty much same as AYA and adult except no Esphall (like in AYA), and added EWALL)
ALL tx MRD >0.1%
Blinatumomab at ~3month mark if MRD+, follow with allo HCT (regardless of whether or not MRD+ after blinatumomab)
3 months!!!/3 cycles!! Not just after induction!!
Cytokine release syndrome tx
Tocilizumab +/- dex
*be more aggressive if CAR-T. If blinatumomab you can just stop infusion for mild reactions
ICANS treatment
Grade 1: supportive care
Grade 2: dex x1
Grade3-4: Dexamethasone 10 mg IV Q6h or Methylprednisolone 1 mg/kg iv q12h
no tocilizumab
Ppx CAR-T therapy pts with keppra x30 days
When to do iron chelation
MDS requiring >20 transfusions and serum ferritin >2500 ng/mL
goal ferritin <1000
ALL maintenance
-Backbone of 6MP + weekly MTX with periodic vincristine or prednisone
-continue for 1-2y
-omit for mature B-cell ALL
Non-heme indications for BMT
Neuroblastoma, Ewings, brain tumors, germ cell, testicular
CLL without del(17p)/TP53: first line tx
preferred
-Acalabrutinib +/- obinutuzumab
-venetoclax + obinutuzumab
-zanubrutinib
other
-ibrutinib (cat 1)
-consider chemo immunotherapy (bendamustine, Chlorambucil, obinutuzumab)
IGHV mutation >2%, <65 y, and fit
-FCR (Fludarabine, cyclophos, rituxan)
Note: don’t need to start rx right away I’m asymptomatic patients RAI stage 0 or Binet stage A
Note: venetoclax based is fixed duration (1 yr) as opposed to indefinite like BTK inhibitors
-obinutuzumab is only 6 months when given with BTK-I
CLL without del(17p)/TP53: second line tx
preferred
-Acalabrutinib
-venetoclax (2y) + rituximab (6 mo)
-zanubrutinib
other
-ibrutinib (cat 1)
-venetoclax
-consider repeating ven + obin if remission achieved in first line
-chemo-immunotherapy (BR, R2, FCR, obinutuzumab)
Note: venetoclax based is fixed duration (2 yr) as opposed to indefinite like BTK inhibitors
Use opposite of what you used before (BTK-I vs venetoclax)
CLL third line
Without del(17P)TP53 mutation
-pirtobrutinib
PI3K inhibitors
-duvelisib
-idelalisib +/- rituximab
Chemotherapy or immunotherapy
-bendamustine + rituxan (<65 and fit)
-FCR (<65 and fit)
-Lenalidomide +/- rituximab
-obinutuzumab
With del(17P)TP53 mutation
-pirtobrutinib
PI3K inhibitors:
-duvelisib
-idelalisib +/- rituximab
-alemtuzumab +/- rituximab
-HDMP + anti-CD20 mAb
-Lenalidomide +/- rituximab
Lisocabtagene
Allo HCT???
CLL with del(17p)/TP53 mutation: first line tx
preferred
-Acalabrutinib +/- obinutuzumab
-venetoclax + obinutuzumab
-zanubrutinib
no chemo-immunotherapy
Note: don’t need to start rx right away I’m asymptomatic patients RAI stage 0 or Binet stage A
Note: venetoclax based is fixed duration (1 yr) as opposed to indefinite like BTK inhibitors
-obinutuzumab is only 6 months when given with BTK-I
CLL with del(17p)/TP53 mutation: second line tx
preferred
-Acalabrutinib
-venetoclax + rituximab
-venetoclax
-zanubrutinib
Note: venetoclax based is fixed duration (1 yr) as opposed to indefinite like BTK inhibitors
Use opposite of what you used before (BTK-I vs venetoclax)
When is IVIG indicated
Consider in CLL when serum IgG <500 mg/dL AND recurrent (2+ in 6
Months) sinopulmonary infections requiring IV ABX or hospitalization
Does not improve OS
Multiple myeloma IgG<400 and recurrent life threatening infections
may cause false positive hep b core antibody
Hairy cell leukemia
If tx is indicated
-cladrabine +/- rituximab
-pentostatin
If unable to tolerate purine analog (frail or active infection): vemurafebib +/- obinutuzumab
Don’t forget pjp and hsv ppx
Remember BRAFV600E mutation
Relapsed/refractory hairy cell leukemia
Relapse >2 years:
-cladrabine + rituximab
-pentostatin + rituximab
-Rituximab
Relapse <2 years:
-alternative purine analog + rituximab
-vemurafenib +/- rituximab (preferred if BRAF mutation)
-Dabrafenib + trametinib (also preferred is BRAF mutation and not already tx with BRAF-I)
Third line
-vemurafenib +/- rituximab (preferred if BRAF mutation)
-Dabrafenib + trametinib (also preferred is BRAF mutation and not already tx with BRAF-I)
-ibrutinib
-zanubrutinib
-venetoclax +/- rituximab
Note: moxetumomab removed from market in July 2023
CML (chronic phase) first line
Low risk:
-imatinib 400 QD
-dasatinib 100 QD
-nilotinib 300 bid
-bosutinib 400 QD
Intermediate-high risk (same doses)
-dasatinib
-nilotinib
-bosutinib
-imatinib but only one that isn’t cat 1
base choice on ADRs and comorbidities
Note: maybe prefer a second gen over imatinib in woman who want a rapid and deeper response with eventual TKI discontinuation for family planning purposes
CML (chronic phase) second line
-nilotinib, dasatinib, bosutinib
(Switch to a different one if used before)
not imatinib
Same doses as first line
CML (chronic phase) third line
-omacetaxine mepesuccinate
-Ponatinib 15-45 mg QD
-asciminib 40 bid or 80 QD
-allogenic HCT
CML T315I mutation
-ponatinib (preferred)
-omacetaxine
-asciminib 200 BID (use instead of Ponatinib if CV risk fxs)
-allogenic HCT
Note: this mutation is associated with secondary TKI resistance
CML accelerated phase
basically tx like second or third line chronic phase- except NO ASCIMINIB, and doses are different
-second gen TKI or alternate second gen TKI
-Ponatinib if no other tki indicated
-omacetaxine if resistant to 2+ tki-NOT FOR DE NOVO ACCELERATED PHASE (don’t get tripped up)
-allo HCT (if able to first achieve chronic phase)
Doses
-imatinib 600-800 QD (probably wouldn’t use though)
-dasatinib 140 QD
-nilotinib 400 bid
-bosutinib 500 QD
-Ponatinib 45 QD
CML Blast phase
BCR-ABL TKI + induction tx of respective type of acute leukemia (could be ALL or AML)
-DONT USE IMATINIB UNLESS NO OTHER CHOICE
-if second chronic phase is achieved- allogenic HCT
-CNS ppx if lymphoid type
-dasatinib preferred in CNS of lymphoid type
DCIS
-BCS +/- RT or total mastectomy +/- reconstruction
Follow by: endocrine therapy x 5y (if for BCS and HR+)- decreases risk or ipailateral or contralateral BC
notice BCS does not require RT here
2 mm margin
When to give RT in early stage breast cancer
- If BCS
- If total mastectomy:
-LN+ OR T>5 cm (T3)
-no RT if negative margins
give RT after chemo if chemo is given
-no RT if TP53 mutation
CLL with bleed risk or on AC
Venetoclax based regimen preferred over BTK inhibitor
CML with bleed risk or on AC
Avoid Ponatinib and dasatinib
Follicular lymphoma: contiguous stageI-II (grade 1-2)
ISRT preferred
Could do ISRT +/- (mAb +/- chemo)
Follicular lymphoma: non-contiguous stage II (grade 1-2)
Anti-CD20 mAb +/- chemo +/- ISRT
Follicular lymphoma: stage III-IV (grade 1-2)
-bendamustine + rituximab/obinutuzumab (probably choose over R-CHOP)
-CHOP + rituximab/obinutuzumab (for more aggressive dx or grade 3)
-CVP + rituximab/obinutuzumab
-Lenalidomide + rituximab (frail pts)
Elderly/infirm
-rituximab x4 weekly doses (low tumor burden, elderly/infirm) preferred
-Chlorambucil + rituxan
-cyclophos + rituxan
Follow with maintenance if response to frontline therapy:
-Rituximab q8week x2 years (12 doses) (unlike MCL which is 3 yrs) (note only 4 doses of tx with rituxan alone)
-obinutuzumab 1000 mg q8wk x2yr (12 doses)
Follicular lymphoma: stageI-IV (grade 3)
Grade 3A: controversial
Grade 3B: Tx like DLBCL- (R-CHOP)
Maintenance for follicular lymphoma
Whatever CD-20 mAb was given frontline
-Rituximab q8week x2 years (12 doses) (unlike MCL which is 3 yrs) (note only 4 doses of tx with rituxan alone)
-obinutuzumab 1000 mg q8wk x2yr (12 doses)
if response to frontline therapy
Follicular lymphoma: second line
same as stage III-IV (grade 1-2)
-bendamustine + rituximab/obinutuzumab
-CHOP + rituximab/ obinutuzumab
-CVP + rituximab/obinutuzumab
-Lenalidomide + rituximab
choose depending on fitness, prior tx, and early vs late relapse: *early relapse (<2y AKA POD24) or fitter pts should be tx more aggressively
Elderly/infirm
-rituximab x4
-Chlorambucil +/- rituximab
-cyclophosphamide +/- rituximab
-tazametostat (second line only)
Consolidation
-rituximab - EVERY 12 WEEKS (unlike 1st line-q8wk) x 2 yr
-obinutuzumab every 8 weeks x2yr
-autoor allo HCT
Note: ensure FL is not transforming to a more aggressive lymphoma
Follicular lymphoma: third line
-Copanlisib (PI3K) (NOT others)-(withdrawn)
-CAR-T (axicabtagene, tisagenlecleucel, lisocabtagene)
-tazametostate (irrespective of EZH2 mutation)
-BiTE (mosotuzumab, epcoritamab)
DLBCL based on stage and grade
-stage I-II (non-bulky): R-CHOP x3
Then interim staging:
-CR: R-CHOP x1 or ISRT
-PR: R-CHOP x1-3 +/- ISRT
Or Pola-R-CHP (smIPI>1)
-stage I-II (bulky): R-CHOP x6 +/- ISRT
Or Pola-R-CHP (smIPI>1)
-stage II (extensive mesenteric dx or stage III-IV: R-CHOP x6
Or Pola-R-CHP (IPI 2+)
no maintenance rituximab (unlike follicular lymphoma)
we still do interim staging after ~3 cycles for all stages, but this doesn’t effect tx like it does for stage 1-2 non-bulky
Negative prognostic fxs:
-age > 60
-st III-IV
-extranodal dx > 1 site
-ECOG 2+
-high LDH
DLBCL in elderly or HF
Poor LVEF:
-DA-R-EPOCH (keep dox at base dose)
-R-CDOP
-R-CEPP
-R-CEOP
-R-GCVP
>80 w/ comorbidities
-R-CDOP
-R-CEPP
-R-mini-CHOP
-R-GCVP
More aggressive tx DLBCL (young/fit) or double/triple hit- stage II w/ extensive mesenteric dx or stage III-IV
-DA-R-EPOCH (not appropriate for everyone)
-R-hyper-CVAD
-R-CODOX-M/R-IVAC
-R-mini-CHOP (elderly/frail)
May need auto HCT
give CNS ppx
R-CHOP has inferior outcomes
Note: R-EPOCH has higher rates of neuropathy and febrile neutropenia than R-CHOP
Lymphoma CNS ppx and tx
Ppx: IT MTX x4, systemic MTX x2, or Cytarabine
-DLBCL with IPI score of 4+
-high grade B-cell lymphoma
-Burkitts lymphoma
-HIV lymphoma
-testicular
-MYC, BCL2/6
-primary cutaneous DLBCL
-stage le DLBCL of breast
Tx: systemic MTX +/- IT MTX or Cytarabine
If parenchymal dx tx with systemic HD-MTX
R/R DLBCL
>12 months HCT eligible:
-R-ICE, R-DHAP, R-GDP, other: R-ESHAP, R-gem-ox, R-MINE
-if response: auto HCT +/- ISRT
-if partial response: auto HCT or car-T (all 3 CAR-T ok here)
>12 months HCT ineligible:
Preffered
NOTE: can omit rituximab in below regimens if relapse after <6 months
-polatuzumab vedotin +/- bendamustine +/- rituximab
-tafasitimab + Lenalidomide
-lisocabtagene
Other
-gem/ox +/- R
-GDP +/- R
-CEOP +/- R
-Rituximab
-Lenalidomide + rituximab
<12 months or primary refractory
CAR-T (may need something else in interim)
-axicabtagen ciloleucel
-lisocabtagene maraleucel
DLBCL third line
CAR-T
-axicabtagene
-lisocabtagene
-tisagenlecleucel (not second line option like the other two)
BiTE- AFTER 2 LINES IF THERAPY
-epcoritamab
-Glofitamab
Others
-Loncastuximab tesirine
-Selinexor (after transplant or CAR-T)
Mantle cell lymphoma: Stage II (bulky), III, IV: (aggressive- for young pts with good PFS)
induction
-R-DHA + platinum, followed By R-CHOP in no CR (Lyma regimen)
-alternating R-CHOP/R-DHAP
-Nordic regimen (R-maxi chop alt w/ HDAC)
-R-HyperCVAD (“other” regimen)
-BR —> R + HD-Cytarabine
-Triangle (alt R-CHOP, BTK-I/DHA, platinum)
Consolidation
-ASCT
Maintenance (start after ASCT)
-* covalent BTK-I (ibrutinib preferred) x2y* + rituximab q8 weeks x 3 years (unlike FL which is 2 years)
-notice how this differs from non-aggressive tx where you only do rituximab if they got R-CHOP and there no BTK-I
Mantle cell lymphoma: Stage II (bulky), III, IV: (less aggressive- for older pts or poor PFS)
induction
-BR
-VR-CAP
-R-CHOP
-Lenalidomide + rituximab
-Other: RBAC500 (Ritux, bendamustine, Cytarabine)
consolidation
-rituximab q8 weeks x2-3y (only if they got R-CHOP, cat 2 if given after BR)!!!!! (unlike FL, and aggressive tx of MCL)
Notice no ASCT like with aggressive
Burkitts lymphoma
Low risk:
-CODOX- M +/- R x3 cycles
-DA-R-EPOCH (x3 min, 1 additional after CR)
-R-HyperCVAD alternating with R-MTX/Cytarabine, lnclude IT MTX
High risk:
-CODOX-M alternating w/ IVAC +/- R x4 cycles
-hyperCVAD alternating with R-MTX/Cytarabine, include IT MTX
-DA-R-EPOCH (if can’t take aggressive tx)
>60 years old:
-DA-R-EPOCH (x3 min, 1 additional after CR)
CNS PPX
Second line
-clinical trial preferred
-DA-R-EPOCH
-R-ICE
-R-IVAC
-R-GDP
-HiDAC + rituximab
-HCT
Note: if CNS dx- it should be addressed with initial regimen (give CNS portion first)
Cutaneous T-Cell lymphomas
Pruritis:
-topical moisturizer/emollients
-topical steroid
-TCA, gabapentin, antihistamine
-refractory: aprepitant, naltrexone, mirtazapine, SSRI
Infection ppx:
-avoid central lines
-diluted bleach bath (1tsp/gal or 1/2 cup)—>moisturize
-mupirocin, dicloxacillin, cephalexin if staph colonization
-HSV/VZV reactivation (consider ppx)
-gram negative rods in necrotic tumors
-empiric ABX could include gram neg and gram pos
Stage IA
-topicals: steroid, mechlorethamine, retinoids (bexarotene, tazarotene), imiquimod, phototherapy, RT
Stage IB-IIA
-phototherapy (PUVA), total skin electron beam therapy,
May need systemic tx
Stage IIB-IV
-various combos
Systemic therapy includes:
-alemtuzumab
-bexarotene
-Brentuximab
-Gemcitabine
-interferon
-mogamulizumab
-liposomal dox
-pralatrexate
-romidepsin
-vorinostat
Notice: single agents preferred (unlike peripheral T-cell lymphomas which often require combo
Peripheral T-cell lymphoma tx
-CHOP-21
-CHOEP
-DA-EPOCH
-CHP + Brentuximab vedotin (preferred regimen if CD30+, category 1 for ALCL- anaplastic large cell lymphoma)
no rituximab- there’s no CD20
First line consolidation
-consider HD chemo and ASCT
Second line Relapsed, or 1st line palliative
-Belinostat
-Brentuximab vedotin (if CD30+)
-romidepsin
-pralatrexate
Classic Hodgkin’s lymphoma stage I and II
favorable (non-bulky)
ABVD x2 followed by:
-ISRT
-AVD x4 (deauville 1-3)
-ABVD x1-2 +/-ISRT (deauville 4-5)
-biopsy (deauville 4-5)
-***Elderly/low PFS: A(B)VD x2 +/- AVD x2 + ISRT (preferred)
-CHOPx4 + ISRT
unfavorable (bulky or B-symptoms, and other)
ABVD x2 followed by:
-AVD x4 (deauville 1-3)
-ABVD x2 + ISRT (deauville 4-5, NCCN says 1-3)
-BEACOPP x2-4 +/- ISRT (deauville 4-5)
-Elderly/poor pfs: A(B)VD x2 -> AVD x4 if pet neg
-BV->AVD, conditionally followed by BV
-CHOP x6 +/- ISRT
Note: don’t dose reduce if low counts
Avoid BEACOPP and Brentuximab vedotin in pts >60
Bulky is >10 cm
Classic Hodgkin’s lymphoma stage III-IV
- ABVDx2 followed by:
-AVD x4 (good response-deauville 1-3)
-BEACOPP x3-4 +/- ISRT (if poor response- deauville 4-5) - A + AVD (Brentuximab vedotin + AVD) give with G-CSF- not for pts >60 or with baseline neuropathy
Nivo + AVD?
-Elderly/poor pfs: A(B)VD x2 -> AVD x4 if pet neg
-BV->AVD, conditionally followed by BV
-CHOP x6 +/- ISRT
Note: don’t dose reduce if low counts
Avoid BEACOPP and Brentuximab vedotin in pts >60
R/R classic Hodgkin’s lymphoma
Goal is still CURE!
Chemo +/- ASCT —> followed by Brentuximab vedotin in high risk pts
Chemo options are:
-ICE
-IGEV
-ESHAP
-MINE
-GVD
-bendamustine
-Brentuximab vedotin +/- bendamustine (unless BV was used in frontline)
-Brentuximab vedotin maintenance x1y
-nivo or pembro after ASCT +/- Brentuximab vedotin or if can’t get ASCT (EBV and Reed-sternberg cells express PD-L1)
Other options include: everolimus, Lenalidomide, nivolumab +/- BV, pembro +/- GVD
Nodular lymphocyte predominant Hodgkin’s lymphoma
Stage IA, IIA, (non-bulky)
-ISRT (preferred)
-observation
Stage IB, IIB, or IA, IIA (bulky), III, IV
-R-ABVD + ISRT
-R-CHOP + ISRT
-RCVbP + ISRT
-rituximab
rituximab if CD-20 (only time it’s used in HL
no Brentuximab vedotin (no CD30)
R/R
-rituximab
-R-bendamustine
-R-DHAP
-R-ICE
-R-IGEV
-Indolent course and late relapse (decades later)
-no Reed-Sternberg cell
Note: bulky is >10 cm
Good Prognosis
Follicular lymphoma: asymptomatic or minimal symptoms
-Don’t need tx right away! Even for later stage!
-unless early stage- give RT bc it may actually be curable
Indications to tx:
-symptomatic dx
-end organ dysfunction
-cytopenias
-massive bulk or splenomegaly
-steady progression over 6 months
-recurrent infxns
-pt preferred
If asymptomatic don’t tx
Waldenstrom macroglibulinemia (lymphoplasmacytic lymphoma)
Dont need to tx right away (like FL), see below
-BR (bendamustine + rituximab)
-bortezomib + dex + rituximab (other)
-ibrutinib +/- rituximab (cat 1)
-zanubrutinib (cat 1)
Second line
-any of the above options
-rituximab + cyclophos + dex
Indications to tx
-recurrent fevers, night sweats, wt loss, hyperviscocity, bulk lymphadenopathy, dx related peripheral neuropathy, splenomegaly, hepatomegaly, organomegaly, symptomatic cryoglobulinemia, symptomatic cold agglutin anemia, autoimmune hemolytic anemia, thrombocytopenia (median time to these symptoms in asymptomatic pts (25%) is >10 years)
-level of IgM alone is not enough to start tx
-note can use plasmapheresis if needed to Decrease IgM
Note: pts stratified based on age, B2-microglobulin, LDH, and albumin
Don’t use rituximab alone with IgM>4000 (flare)
hyper-viscosity is often a big issue
Marginal zone lymphoma
Tx similarly to follicular lymphoma
-if EMZL gastric lymphoma- eradicate h. Pylori
-use anti HCV if HCV associated
-SMLZ- rituximab alone is preferred initial option
edit this card if more info from workbook
MGUS and smoldering
Observation
Multiple myeloma: transplant eligible
-VRd: bortezomib + Lenalidomide + dex
-KRd: cardilzomib + Lenalidomide + dex (would use if pt has neuropathy)
-consider 2 drug regimen if old/frail
Other:
Daratumumab + VRd (unlike HCT ineligible)
if renal impairment
-CyBorD- cyclophos + bortezomib + dex
-thalidomide based regimen
Follow with ASCT (Melphalan based)
-if we can get them to at least PR with <10% plasma cells
.
**Then maintenance **
-Lenalidomide 10 mg daily (cat 1)
-bortezomib QOweek (alternative)
-Lenalidomide + velcade? (Consider for high risk)
weekly and SQ velcade preferred
Multiple myeloma: transplant ineligible
category 1
-VRd: bortezomib + Lenalidomide + dex
-daratumumab + lenalidomide + dex
-consider 2 drug regimen if old/frail
Other cat 1s
-KRD
-dara + bort + Melphalan + pred
Others (more frail pts)
-bortezomib + dex
-Lenalidomide + low dose dex
-VRd-lite
Others:
-CyBorD (or thalidomide based if renal issues)
-KcyD
-cyclo+ Len + dex
followed by maintenance
-Lenalidomide 10 mg daily (cat 1)
-bortezomib QOweek (alternative)
-Lenalidomide + velcade? (Consider for high risk)
weekly and SQ velcade preferred
Relapsed/ refractory multiple myeloma
Progression is Increase in M protein of 25%, FLC ratio increase of 10+, or new lesions
-Many options
-ask what has pt already gotten (refractory to) or intolerant to
-can repeat drugs if >6 months later
Early relapse (1-3 prior therapy)
-think second gen PI and IMiDs
-think triple therapy with anti-CD38
-venetoclax + dex t(11;14)
Late relapse and >4 prior therapies
-CAR-T or BiTE (after 4 therapy including PI, IMiD, and anti-CD38)
-ciltacabtagene, idecabtagene, teclistimab, talquetamab, elrantamab
-Selinexor/dex (after 4 therapy- refractory to 2 PI, 2 IMiD, and antiCD38)
-Other: bendamustine based (after 3 therapies)
-Other: belantamab (via compassionate use program)
REMOVED FROM MARKET
-belantamab
-panobinostat
Mantle cell Lymphoma: relapsed
Second line
-Acalabrutinib
-ibrutinib +/- rituximab (not preferred)
-zanubrutinib
-Lenalidomide + rituximab (If BTK CI)
-Radiotherapy if localized relapse (rare)- most radiosensitive NHL FYI
Third line
-brexucabtagene (after BTK and chemoimmunitherapy)
-lisocabtagene
-pirtobrutinib
Consolidation
-consider allogenic HCT (unlike 1st line which is ASCT)
Role of surgery and RT in melanoma
Surgery: all stages
RT: limited role, mostly palliation
Melanoma: resected stage I-II
Stage I-IIA
-observation or clinical trial
Stage IIB-IIC
-pembrolizumab (IIB -IIIC) OR NIVOLUMAB (adjuvant)
-clinical trial
-observation
-locoregional RT
notice no BRAF here
Melanoma: resected stage III
-nivolumab
-pembrolizumab
-Dabrafenib + trametinib (BRAF V600 E or K mutation) IIIA with SLN met >1 mm or st IIIB/C, notice not used before this stage
-observation
Note: BRAF + MEK may have faster onset and benefit than ICI (4-6 wks vs 3 months)
Could also do neoadjuvant if you want
Melanoma: unresectable stage III, satellite with in transit lesion
Talimogene laherparepvec (T-Vec)
Satellite: visible cutaneous or SubQ met within 2 cm of primary
In transit: regional cutaneous or SubQ met >2 cm from primary
Melanoma: metastatic or unresectable (first line)
-nivolumab (cat 1)
-pembrolizumab (cat 1)
-nivolumab + ipilimumab (cat 1) (preferred if asymptomatic with brain mets)
-nivolumab/relatlimab
-pembro + low dose ipilimumab (cat 2B)
BRAF V600 (E or K) mutation
-START WITH IPI/nivo followed by: (unless symptomatic/rapidly growing)
-Dabrafenib + trametinib
-vemurafenib + Cobimetinib
-encorafenib + binimetinib
Note: use BRAF + MEK combo first if needed for high volume symptomatic dx d/t faster onset and benefit (4-6 wks vs 3 months with ICI)
Melanoma: metastatic or unresectable (second line)
Progression defined as 25% increase in tumor burden- 2 observations 4 wk apart
-pembrolizumab
-nivolumab
-nivolumab + ipilimumab
-pembro and low dose ipilimumab
BRAF V600 mutation
-Dabrafenib + trametinib
-vemurafenib + Cobimetinib
-encorafenib + binimetinib
if short relapse use different agents from different class. If progression on monotherapy, try combination. If late relapse after a PR/CR/SD (>3 months) you can repeat same drug or class
Chemo-dont really use ever
-Dacarbazine
-Temozolomide( maybe good if brain Mets) -preferred
-taxanes
-carbo + pacli- preferred (not better than pacli alone but maybe give after TMZ or dacarbazine)
Melanoma: metastatic or unresectable (second or subsequent therapy) of weird mutations
-KIT: imatinib
-NRAS: binimetinib
-NTRK: larotrectenib or entrectinib
Melanoma: stage 1
Surgery
When is RT given for early stage breast cancer?
LN positive or T>5cm
-if BCS (as opposed to mastectomy)
-consider if close/positive margins
Who qualifies for OAS in BC?
-young age, high grade, LN+
-stage II-III eligible for adjuvant chemo
-metastatic with ET- always if premenopausal
-If AI is used in premenopausal or male patient (male pts we prefer tamoxifen alone)
Note: high rates of ADRs/hard to tolerate
Note: Duration is 5 years! After 5 years can continue another 5 of tamoxifen or AI but drop the OAS
Criteria for olaparib in early stage BC
Need GERMLINE BRCA mutation also obviously!!!
Notice: Don’t use if HER-2+, don’t get tripped up
After neoadjuvant
-TNBC: residual dx
-HR+, HER-2(-): residual dx and CPS EG score 3+
After adjuvant
-TNBC: pT2+, pN1+ (like neoadjuvant req)
-HR+, HER-2(-): LN+ 4+
TNBC
Neoadjuvant: residual dx
Adjuvant: pT2+, pN1+
HR+/HER-2(-)
Neoadjuvant: residual dx and CPS EG score 3+
Adjuvant: LN+ 4+
When to do quadruplet regimen for multiple myeloma?
-under investigation: there are deeper responses but we don’t know how long the response will last and if we are wasting our daratumumab up front
-Dara- VRD
-Dara-VTD
-Dara-KRD
Update: probably a good idea in younger pts but in older is probably bad bc of increased deaths.
May be good in high risk features
May use dara- len- dex in older pts
Head and neck locally advanced (T3-T4, N1-N3)
Chemo-radiation
-RT + cisplatin 100 mg/m2 q3weeks x2-3 doses (cat 1)
-RT + Carboplatin + 5FU infusion (cat 1)
Nasopharyngeal
Induction (category 1 for EBV associated nasopharyngeal, but could use for non-nasopharyngeal)
-TPF (Taxane (docetaxel) + cisplatin + 5FU) followed by weekly carbo (low dose) + RT
-Gemcitabine + cisplatin (nasopharyngeal only)
Nasopharyngeal non-induction
-cisplatin + RT —> cisplatin + 5FU
Note: more neutropenia with induction
Head and neck early stage (I and II, T1-T2)
Surgery and RT
Chemo-RT with cisplatin + RT ONLY IF
1. Extracapsular nodal extension OR
2. Positive mucosal margins
Head and neck: recurrent/ metastatic
preferred first line
-carbo/cisplatin + 5FU + pembro (non-nasopharyngeal)
-pembro alone (cps 1+) (non-nasopharyngeal)
-cisplatin + Gemcitabine (nasopharyngeal)
-cisplatin + Gemcitabine + pembro/nivo (nasopharyngeal)
-cisplatin + Gemcitabine + toripalimab (nasopharyngeal)
-pembrolizumab (Cat 1 if CPS >1)
other first line
-carbo/cisplatin + 5FU + cetuximab (non-nasopharyngeal)
second line
-nivolumab (non-nasopharyngeal)
-pembrolizumab (non-nasopharyngeal)
-Note: ICI is an option for nasopharyngeal but less strong rec and nivo only for non-keratinizing and pembro needs PD-L1 +
RT
If ECOG 2+ use single agent
-non-nasopharyngeal: pembro, cisplatin, carbo, paclitaxel, docetaxel, 5FU, MTX, capecitabine, cetuximab, afatinib (cat 2)
-nasopharyngeal: all of the same except: add gemzar, subtract pembro and afatinib
Differentiated thyroid cancer
first line
-surgery (thyroidectomy v lobecetomt) followed by RAI
second line
-active surveillance* (if asymptomatic and no brain Mets)
-sorafenib
-lenvatinib (preferred)
subsequent
-cabozantinib
Use these after RAI instead of above recs if applicable
-RET: pralsetinib, Selpercatinib
-BRAFV600E: vemurafenib, Dabrafenib +/- trametinib (Dabrafenib + trametinib combo is preferred)
-(TMB 10+): pembro
-NTRK: larotrectinib, entrectinib
Thyroid: when is RAI NOT recommended after surgery
When is is definitely indicated?
ALL of the following: LOW RISK
-classic papillary carcinoma
-largest primary tumor <2 cm
-intrathyroidal
-unifocal or multifocal primary papillary tumor 1 cm or less
-no detectable Tg- antibodies
-post-op un-stimulated Tg< 1
-negative post-op ultrasound
Any of the following
-gross extra thyroidal extension
-primary tumor >4 cm
-post-op unstimulated Tg>10
-indicates biochemical recurrence
-bulky or >5 LN +
Medullary thyroid carcinoma
-surgery- total thyroidectomy (DTC can often get away with just lobectomy)
-RT for residual dx
Recurrent or advanced
-RET-wild type:
-cabozantinib CAPSULES
-Vandetanib-REMS
-RET-mutant:
-Selpercatinib
-pralsetinib
Anaplastic thyroid carcinoma
Preferred
-Dabrafenib + trametinib (BRAFV600E mutation)
-Selpercatinib, pralsetinib (REt fusion)
Other
-Carboplatin + paclitaxel
-docetaxel + doxorubicin
-paclitaxel
-doxorubicin
Clinical trials if able
Thyroid cancer TSH suppression
High risk recurrence or residual dx
-goal <0.1
Low risk dx recurrence (no e/o dx on imaging)
-goal 0.1-0.5
-use levothyroxine
-don’t do this for MTC
-supplement with calcium 1200 mg/day and vit D 1000 units/day
ADT therapy for prostate cancer
-Start with LHRH agonist (or antagonist). Add antiandrogen later (CAB) if necessary.
-don’t use antiandrogen monotherapy
-note: first generation antiandrogens are usually only used to prevent tumor flare (1 week before and ~2 weeks after starting LHRH agonist)
Early Prostate adjuvant therapy: when to add ADT? Abiraterone?
ADT: LN positive at time of surgery
Abiraterone: very high risk: 2 of 3 criteria
-PSA >40
-extra-prostatic extension
-Gleason of 8 or more
Small cell lung cancer- limited stage (stage I-III)
-surgery (in some cases- T1-T2w/o mediastinal pathology, T3 based on size, N0, may consider)
-RT + cisplatin + etoposide x4 cycles
-ppx cranial RT for pts in CR/PR (THIS IS SOC UNLIKE IN extensive stage)
Notice just cisplatin here (unlike extensive stage which is carbo or cisplatin)
Notice no immunotherapy here, unlike extensive stage
Smoking is #1 risk factor
Can now consolidate with Durvalumab like NSCLC
Small cell lung cancer- extensive stage (Stage IV)
-cisplatin/carbo + etoposide +/- immunotherapy q21 days x4-6 cycles followed by immunotherapy maintenance (notice not using RT here like in limited stage)
-consider ppx cranial radiation (consider adding memantine during and after)- NOT SOC LIKE LIMITED STAGE
Notice both carbo and cisplatin okay here (unlike limited stage- just cisplatin
-use atezolizumab or Durvalumab
-Durvalumab changed from q21d to q28d in maintence
-consider chest RT for residual thoracic dx
-if positive brain Mets: (RT before chemo if symptomatic, otherwise chemo first
Second line
-if recurrence only in brain and systemic dx stable- refer to radiation!!
-rechallenge with same regimen (minus ICI)!!! If CHEMO FREE x6 months (consider for 3-6 mo)
-lurbinectedin 3.2 mg/m2- (NO BRAIN METS!)
-topotecan 1.5 IV or 2.3 PO mg/m2
-Irinotecan
-clinical trial
-pacli, doc, TZM, CAV, etop, Vinorelbine, gem, nivo, pembro
-avoid immunotherapy if progressed on maintenance!! Just repeat platium doublet if chemo sensitive
Note: CSFs not recommended in patients receiving thoracic RT with chemo (cat 1 rec)- increased risk of pulmonary toxicity
Smoking is #1 risk factor
Early stage NSCLC: adjuvant therapy overview (IA-IIIA)
IIIB IS SEPARATE
Stage IA
N: observation
P: resection
Stage IB-IIA
N: observation, chemo for high risk, or osimertinib
P: re-resection or RT +/- chemo
stage IIB
N: chemo FOLLOWED BY atezolizumab, OR osimertinib
P: resection + chemo, or chemoradiation
Stage IIIA
N: chemo + atezolizumab, OR osimertinib, OR sequential chemo and consider RT
P: chemoradiation
-N- negative margins
-P- positive margins
-Osimertinib- use when EGFR exon 19 deletion or exon 21 L858R, tx x3 yrs
-chemo is platinum doublet
-non-squamous: cis + pem
-squamous: cis + gem, or cis + doc
-IB-IIA high risk: poorly differentiated, vascular invasion, wedge resection, tumor >4cm, visceral pleural involvement, unknown LN status
Atezolizumab: completely resected IIB-IIIA or high risk IIA w/ PDL1 1%+
Pembro: also and option now, for high risk IIA-IIIA regardless of PDL1- give AFTER chemo
-osimertinib- give AFTER chemo unless ineligible for chemo
Durvalumab consolidation x12 months for unresectable stage II or III
_______________________________________
-If supracalvicular or contralateral LN positive can NOT do surgery
-R0 is goal after surgery (no residual dx), or R1 or R2 there’s dx left over (positive margins essentially)
-in LN +, or if >4cm LN negative we will usually need some adjuvant tx
Early stage NSCLC- neoadjuvant-
1. Who qualifies?
2. Which regimens?
For resectable tumors: 4+ cm OR LN positive
-Nivolumab + platinum doublet q3 weeks x3 cycles
-Any histology: carbo + pacli
-Non-squamous: cis + Pemetrexed
-Squamous: cis + Gemcitabine
Pembro + platinum doublet every 3 weeks x4 cycles—> adjuvant pembro
-Non-squamous: cis + Pemetrexed
-Squamous: cis + Gemcitabine
Dostarlimab + platinum doublet every 3 weeks x4 cycles
-non-squamous: cis/pem
-squamous: carbo/pacli, cis/gem
NSCLC- Stage IIIB (goal is to downstage for resection)
Chemo + radiation (I.e., no surgery like earlier stages)
Non-squamous:
-cisplatin/carbo + pemetrexed + RT
All histologies:
-carbo + paclitaxel + RT
-cisplatin + etoposide + RT
Durvalumab consolidation x12 months for unresectable stage II or III
NSCLC consolidation
Durvalumab consolidation x12 months for unresectable stage II or III -PFS 0-1
-No dx progression after 2+ cycles of definitive chemoradiation
Advanced NSCLC first line actionable mutations
Non-squamous- AAAHHH WTF DONT MISS THIS!!
First line:
-EGFR Exon 20 insertion: Amivantamab + Carboplatin + pemetrexed (amivantamab monotherapy if progression on this)
-EGFR exon 19 del- osimertinib (option to give with platinum doublet if nonsquamous)
-EGFR L85R- osimertinib
-EGFR S768I, L861Q, or G719x- afatinib or osimertinib
-ALK- alectinib, Brigatinib, lorlatinib
-ROS1- entrectinib (esp if brain Mets) crizotinib, repotrectinib
-MET exon 14 skipping- capmatinib, tepotinib
-RET-Selpercatinib, pralsetinib, (Cabozantinib sometimes)
-BRAFV600E- Dabrafenib + trametinib or encorafenib + binimetinib
-NTRK: larotrectinib, entrectinib
-PDL1 (other mutations take precedence)!!!!!
SECOND LINE (failed 1st line targeted):
-SYMPTOMATIC after osimertinib: amivantamab, Carboplatin, pemetrexed (Cat 1)
-EGFR: erlotinib +/- bevacizumab or ramucirumab, afatinib, dacomitinib, gefitinib —>chemo (NOT ICI) if further progression
-ALK: lorlatinib (progressed on alectinib, Brigatinib, ceritinib
-progressed on crizotinib: alec, lorlat, brigat, ceritinib
-progressed on two ALK: lortalinib (but —>after that we need chemo +/- ICI)
ROS1: if progressed on entrectinib, crizotinib, ceritinib, consider lorlatinib
-progressed on crizotinib- entrectinib
-Reprotrectinib- prior ROS1
MET exon 14 skip: if progress on above go to chemo +/- ICI
NTRK: if progress on above go to chemo+/- ICI
BRAF: if progress on above go to chemo +/- ICI
-Further progression warrants change to ICI +/- chemo for all classes except EGFR (just chemo)
-don’t use ICI with targeted therapy
Squamous-AHHH WTF DONT MISS THIS!!
First line:
-PDL1
Advanced Non-squamous NSCLC (no actionable mutation, PS0-2)
PD-L1 50%+
-monotherapy: pembro, atezolizumab, of cemiplimab
-CAN ALSO USE COMBOS BELOW
PD-L1 1-49% (or regardless of PDL1)
-platinum doublet with (pemetrexed, bevacizumab, nab-paclitaxel) + pembro/cemip followed by I/O maintenance (see maintenance notecard)
-ipilimumab + nivolumab + pemetrexed + platinum —>IPI/nivo
-ipilimumab + nivolumab (ASCO disagrees)
Notice, atezolizumab only used as monotherapy, not PREFERRED in combos! (There is one cat 1 option for atezolizumab/bevacizumab/carbo/paclitaxel—unlike squamous), this is also the only regimen BEVACIZUMAB is used with ICI)
Note: cisplatin/carbo + pemetrexed + pembro—>pembro is preffered
Category 2 options
Tremelimumab + Durvalumab + chemo (platinum doublet) followed by tramelimumab x1 and Durvalumab q4wk
Note: if there is an actionable mutation, always target this first before ICI
Contraindication to ICI
-platinum doublet with (paclitaxel, nab-paclitaxel, docetaxel, etoposide, Gemcitabine, pemetrexed) +/- bevacizumab (w/ pem or pacli regimen)
-Gemcitabine + (docetaxel or Vinorelbine)
Advanced squamous NSCLC (no actionable mutation, PS0-2)
PD-L1 50%+
-monotherapy: pembro, atezolizumab, of cemiplimab
-CAN ALSO USE COMBOS BELOW
PD-L1 1-49% (or regardless of PDL1)
-platinum doublet with (paclitaxel, nab-paclitaxel) + cemiplimab/pembro followed by I/O maintenance (see maintenance notecard)
-ipilimumab + nivolumab + paclitaxel + platinum —>IPI/nivo
-ipilimumab + nivolumab (ASCO disagrees)
notice no Pemetrexed or bevacizumab for squamous
Notice, atezolizumab only used as monotherapy, not in combos! (unlike non-squamous where there are a few exceptions)
Note: cisplatin/carbo + pacli or nab-pacli + pembro is preffered
Category 2 options
Tremelimumab + Durvalumab + chemo (platinum doublet, could use Gemcitabine for squamous) followed by tramelimumab x1 and Durvalumab q4wk
Contraindication to ICI
-platinum doublet with (paclitaxel, nab-paclitaxel, docetaxel, etoposide, Gemcitabine)
-Gemcitabine + (docetaxel or Vinorelbine)
Advanced NSCLC maintenance therapy
After 4-6 cycles of chemo in pts with response or stable dx
Continuation: (continue part of initial regimen)
-pembro +/- pemetrexed
-bevacizumab
-pemetrexed +/- bevacizumab
-atezolizumab +/- bevacizumab
-cemiplimab +/- pemetrexed
-ipi + nivo
-there are other options but these are category 1
Switch:
- Pemetrexed
NOTE: maintenance is ONLY for STAGE IV, unlike consolidation with Durvalumab which is stage II-III
Advanced NSCLC second line actionable mutations- These are given AFTER CHEMO +/- ICI (besides exceptions)
These are given after CHEMO
ERBB2 (HER-2): fam-trastuzumab deruxtecan
-other: ado-trastuzumab emtansine
KRAS G12C: sotorasib, adagrasib
Exon 20 insertion: amivantamab if not already used is an option
After initial therapy but before chemo +/- ICI
-T790M: osimertinib (if not used first line) (resistance mutation)
-EGFR mutated leptomeningeal dx: osimertinib
don’t use ICI with targeted therapy
Advanced NSCLC subsequent therapy (after second line targeted therapies if applicable)
No prior I/O-chemo only (unlikely):
-nivolumab (regardless of PD-L1
-pembro (PD-L1 >1%)
-atezolizumab (regardless of PD-L1)
Regardless of prior I/O
-pemetrexed (non-squamous)
-docetaxel
-nab-paclitaxel
-Gemcitabine
-docetaxel + ramucirumab (unlike gastric/esophageal which is pacli)
-trastuzumab deruxtecan (HER-2+)
Dont repeat immunotherapy if progressed on immunotherapy
Note: if progression on EGFR inhibitor-second line chemo preferred over ICI
Hepatocellular carcinoma: non-metastatic
Resectable
-resection—> OBSERVATION (no adjuvant tx)
Unresectable
-transplant (AFP<1000 AND <5 cm or 2-3 tumors <3 cm)
-locoregional therapy (if transplant ineligible)- ablation, arterial embolization +/- chemo, radiotherapy
-systemic therapy
-supportive care
Hepatocellular carcinoma: metastatic
First line
-atezolizumab + bevacizumab (child Pugh A only)
-Tremelimumab x1 + Durvalumab q4wk
Other category 1
-sorafenib (child Pugh A or B7)
-lenvatinib (child pugh A) (less palmar-plantar erythro… than sorafenib)
-durvalumab
-tislelizumab
Subsequent (all child Pugh A)
-regorafenib
-Cabozantinib (tablets)
-ramucirumab (AFP>400)
Note: beware of bevacizumab if variceal bleeding!/Varices!
Pancreatic cancer: resectable
Adjuvant (resectable)
-mFOLFIRINOX (ECOG 0-1) (notice it’s modified)
-Gemcitabine + capecitabine
Other cat 1:
-Gemcitabine
-5FU/leucovorin
Neoadjuvant (borderline resectable)- 4-6 cycles
-FOLFIRINOX/ mFOLFIRINOX (option for BRCA1/2 or PALB2 mutations)
-Gemcitabine + nab-paclitaxel
-Gemcitabine + cisplatin (only for BRCA 1/2 or PALB2 mutations)
-give 2-6 cycles
-may follow with chemoradiation
Pancreatic cancer: locally advanced AND metastatic
Good PFS- ECOG 0-1
-FOLFIRINOX/ mFOLFIRINOX (option for BRCA1/2 or PALB2 mutation)
-NALFIROX (as above but uses liposomal irinotecan)
-Gemcitabine + nab-paclitaxel
-Gemcitabine + cisplatin (only BRCA 1/2 or PALB2 mutation)
-other:
Gemcitabine + erlotinib (metastatic)- highly toxic (cat 1)
-Gemcitabine (metastatic)- (cat 1)
Intermediate PFS
-Gemcitabine + nab-paclitaxel (ECOG 2)
-capecitabine
-Gemcitabine
Poor PFS
-Gemcitabine (standard (cat1)or FDR)
-capecitabine (cat 2B)
-continuous infusion 5FU (cat 2B)
Follow with maintenance if response or stable dx x4-6 months- us PARP if BRCA of PALB2, or carry forward part of original regimen
Pancreatic cancer maintenance
Prior platinum containing regimen
-Olaparib (if germline BRCA 1/2 mutation)
-Rucaparib (if germline or somatic BRCA 1/2 or PALB2)
First line FOLFINOX/ mFOLFIRINOX
-capecitabine (Preferred)
-5FU +/- irinotecan
-FOLFOX
First line Gemcitabine + nab-paclitaxel
-modified Gemcitabine + nab-paclitaxel
-Gemcitabine
maintenance is after response or stable dx x4-6 months (16 weeks) each cycle of chemo is 2 weeks
Pancreatic cancer: second line
Prior fluoropyrimidine based
-Gemcitabine
-Gemcitabine + nab-paclitaxel
-Gemcitabine + cisplatin (BRCA 1/2 or PALB 2 only)
-Gemcitabine + erlotinib
-5FU + liposomal irinotecan (no prior irinotecan)
-Gemcitabine + nab-paclitaxel + cisplatin (cat 2B)
Prior Gemcitabine based
-5FU + liposomal irinotecan (cat 1)
-FOLFIRI
-FOLFIRINOX/ mFOLFIRINOX
-fluoropyimidine + Oxaliplatin
-capecitabine
-continuous 5FU
Targetable
-pembro (MSI-H, dMMR, TMB 10+)
preferred
-larotrectinib, entrectinib (NTRK)-(preferred)
-Dabrafenib + trametinib (BRAFV600E)
-Selpercatinib (RET)
-Adagrasib/ sotorasib (KRASG12C)
-chemoradiation (other)- locally advanced
Note:
-pembro or NTRK preferred over chemo if appropriate
-single agent chemo if poor PFS
Gastric cancer: localized
T2+ or any LN involvement
Peri-operative chemo:
-FLOT (5FU + leucovorin + Oxaliplatin + docetaxel) (preferred cat 1)
-fluoropyrimidine + Oxaliplatin (preferred)
-5FU + cisplatin
Note: can also consider the following but NOT category 1
-pre or post-operative chemo-RT
-neoadjuvant or perioperative immunotherapy (MSI-h/dMMR)
-post-operative chemo: CAPOX is cat 1 (if D2 LN dissection)
Esophageal cancer: localized
Pre-operative Chemoradiation
Preferred
-Carboplatin + paclitaxel- weekly
-5FU + Oxaliplatin (FOLFOX)
Other category 1 regimens
-5FU + cisplatin
Definitive chemoradiation (IF NOT MEDICALLY FIT FOR SURGERY
Preferred
-Carboplatin + paclitaxel
-5FU + Oxaliplatin (FOLFOX)
Other category 1 regimens
-5FU + cisplatin
Peri-operative chemo (ADENO ONLY)
Preferred
-FLOT (5FU + leucovorin + Oxaliplatin + docetaxel) (category 1)
-fluoropyrimidine + Oxaliplatin
Other category 1 regimen
-5FU + cisplatin
Post-operative
-nivolumab (after perioperative chemo-radiation with R0 resection and residual dx)
Note: can also do neoadjuvant or perioperative immunotherapy but not category 1- (MSI-h/dMMR)
oxaliplatin preferred over cisplatin
Gastric: metastatic/recurrent/locally advanced
HER-2 positive
-fluoropyrimidine + oxaliplatin (preferred)/cisplatin + trastuzumab + pembrolizumab (if CPS 1+)
HER-2 negative
-Fluoropyrimidine + Oxaliplatin (preferred)/cisplatin + pembro (if CPS 1+, cat 1 if 10+)/or nivo (if CPS 5+)
MSI-H/dMMR (regardless of CPS
-pembro
-dostarlimab
-nivolumab + ipilimumab
-fluoropyrimidine + oxaliplatin + nivo/pembro
notice difference in CPS rec for nivo compared to esophagel adeno-otherwise it’s the same
For her-2+ cisplatin is category 1 BUT oxaliplatin preferred d/t better tolerability
Esophageal (adenocarcinoma): metastatic/recurrent/locally advanced
HER-2 positive
-fluoropyrimidine + oxaliplatin (preferred)/cisplatin + trastuzumab + pembrolizumab (if CPS 1+)
HER-2 negative
-Fluoropyrimidine + Oxaliplatin (preferred)/cisplatin + pembro (if CPS 1+, cat 1 if 10+)/or nivo (cat 1 if CPS 5+, 2B if CPS<5)
MSI-H/dMMR (regardless of CPS)
-pembro
-dostarlimab
-nivolumab + ipilimumab
-fluoropyrimidine + oxaliplatin + nivo/pembro
notice difference in CPS rec for nivo compared to gastric cancer, otherwise it’s the same
For her-2+ cisplatin is category 1 BUT oxaliplatin preferred d/t better tolerability
Esophageal (squamous cell carcinoma): metastatic/recurrent/advanced
Preferred
-fluoropyrimidine + Oxaliplatin (preferred)/cisplatin +/- nivolumab (cat1)/ pembro (cat 2)
-nivolumab + ipilimumab
MSI-H (regardless of CPS)
-pembro
-dostarlimab
-nivolumab + ipilimumab
-fluoropyrimidine + Oxaliplatin + nivo/pembro
Notice no HER-2 here
oxaliplatin preferred over cisplatin
Gastric and esophageal-adenocarcinoma: subsequent therapies
Second line
Preferred
-ramucirumab + paclitaxel (cat 1) (unlike NSCLC which is docetaxel)
-fam-trastuzumab deruxtecan (HER-2)- (prior tx w/ trastuzumab)
-docetaxel (cat 1)
-paclitaxel (cat 1)
-irinotecan (cat 1)
-5FU + irinotecan
Other
-ramucirumab (cat 1)
Third line
-trifluridine/tipiracil (Lonsurf) (cat 1)
Esophagel squamous cell carcinoma: subsequent therapies
Preferred
-Nivolumab (cat 1)
-pembro if CPS 10+ (cat 1)
-docetaxel (cat 1)
-paclitaxel (cat 1)
-irinotecan (cat 1)
-tislelizumab (cat 1)
-5FU + irinotecan
Maybe prefer chemo over ICI if given both options
Non-melanoma skin cancer
Risk fxs- cumulative sun exposure, age
Other: immunosupression (SCC esp.), hpv, merkel cell polyoma virus (MCC), arsenic, RT, chronic skin inflammation, genetic conditions
-Actinic keratosis: premalignant scc lesion- Tx with retinoids
-nicotinamide: Dec risk SCC
Seems like surgery (Mohs, curettage and electrodessication, excision) is first when able and RT (CI in SLE and XP) if can’t do surgery, then below
CSCC and BCC local
-low risk: curettage + electrodesiccation or excision or RT
-high risk: Excision or Mohs or RT
-topical imiquimod or 5FU if can’t do RT
-chemo not usually used (cisplatin sometimes for CSCC)
BCC locally advanced or metastatic
-vismodegib oral
-sonidegib oral
-cemiplimab (after hedgehog-I)
-note sunscreen does NOT decrease risk for BCC
CSCC locally advanced
-cemiplimab
-pembro
-chemo if can’t do ICI (carbo + pacli)
-cetuximab
-Dont give ICI if transplant patient
MCC
Local:
-adjuvant cisplatin/carbo +/- etoposide in select cases
Advanced:
-clinical trial (preferred)
-avelumab
-pembro
-nivolumab
-chemo if can’t do ICI
-carbo +/- etoposide, teniposide, or CAV
Short answer for advance dx: CSCC and MCC use ICI, BCC use hedgehog
Mantle cell lymphoma Stage I and II (non-bulky)
Stage I or contingious stage II
-ISRT alone
-Less aggressive induction +/- ISRT
Stage II non-contiguous
-Less aggressive induction +/- ISRT
-observation (highly select cases)
Early stage colon cancer
All stages: I, II, III
-surgery (partial colectomy and minimum of 12 LN)
Stage I
-surgical resection followed by surveillance
Stage II
dMMR/MSI-H:
-SURGERY ONLY!! no adjuvant therapy
No high risk factors:
-surgery only (consider adjuvant single agent 5FU or capecitabine)
High risk factors:
-surgery followed by
-capecitabine or 5FU/LV x6 months, or CAPOX X3 mo, FOLFOX x6 mo
Stage III
-surgery followed by
Low risk:
-CAPOX x3 or FOLFOX x3-6 months
High risk (T4 or N2- 4 LN+)
-CAPOX x3-6 or FOLFOX x6 months
-can use neoadjuvant immunotherapy (pembro or nivo +/- ipi) if dMMR/MSI-H (T4b tumors)
Stage 2 high risk factors
-poorly or undifferentiated
-lymphatic/vascular invasion
-bowel obstruction
-<12 LN surgically examined
-perineural invasion
-localized perforation
-close, intermediate, or positive margins
-tumor budding
-T4??
-Note: these risk fxs were not created in the modern era and not everyone agrees that these people need chemo
Note: in high risk stage III there is data supporting stopping Oxaliplatin early after 3 months and ok continue monotherapy to complete 6 months
Early stage rectal cancer
Clinical stage I
-Surgery followed by observation or adjuvant chemo or adjuvant chemo RT
Clinical stage II and III
-TNT (preferred)->surgery->observation
-Neoadjuvant RT->surgery->adjuvant chemo
-Consider neoadjuvant dostarlimab, pembro, nivo for dMMR/MSI-H- THIS IS NOW STANDARD!!
Chemo options
-CAPOX or FOLFOX
-Consider 5FU/LV or capecitabine
-FOLFIRINOX: consider if pT4 or N+
ChemoRadiation options
-RT + capecitabine or 5FU CIVI
-RT + bolus 5FU (consider- NOT PREFERRED)
-Notice no Oxaliplatin with chemo given with RT
note: TNT is neoadjuvant chemo and chemo-RT/or RT
Note: equipoise on whether long or short course RT in TNT is best
Metastatic colorectal cancer (colon or rectal)
First line- INTENSIVE THERAPY
-FOLFOX or CAPOX +/- bevacizumab
-FOLFIRI +/- bevacizumab
-FOLFIRINOX +/- bevacizumab (more aggressive, e.g., R-sided or BRAF)
-FOLFOX (NOT CAPOX) or FOLFIRI + cetuximab or panitumumab (Left sided and RAS/RAF wild type)- EGFR instead of bev (don’t need EGFR mutation)
-pembrolizumab, dostarlimab- NOT NIVO (dMMR/MSI-H)- or IPI/nivo (not preferred)
First line- NON-INTENSIVE THERAPY
-5FU/LV or capecitabine +/- bevacizumab
-cetuximab or panitumumab (Left sided and RAS/RAF wild type)
-pembrolizumab (dMMR/MSI-H)-or IPI/nivo-not preferred
-trastuzumab + (Pertuzumab/ lapatinib/ or tucatinib) (***HER-2+ RAS/RAF wild type)
Note: if single metastatic site to liver or lung: you could do surgery and try to cure- use metastatic regimens though, not typical adjuvant regimens- use CAPOX OR FOLFOX
Notice: FOLFIRINOX NOT FOLFOXIRI
Note: pick EGFR inhibitor over bev if candidate for it
Metastatic colorectal cancer (colon or rectal) subsequent therapy
This card is actually important so don’t skip it
-bevacizumab (can continue from 1st line)
-ziv-afilbercept or ramucirumab: with FOLFIRI or irinotecan (but bevacizumab is preferred)
-cetuximab or panitumumab (RAS/RAF wild type) (unless used in front line)- alone or with FOLFOX or FOLFIRI or irinotecan
-encorafenib + (cetuximab or panitumumab) (BRAF V600E)-need both drugs here (unless used in frontline)
-trastuzumab + (Pertuzumab/ lapatinib/ or tucatinib) (HER-2+ and no prior anti-HER-2 therapy)
-fam-trastuzumab deruxtecan (regardless of prior HER-2 therapy)- progressed on 2 or more likes of therapy!!
-pembro, nivo +/- ipi, or dostarlimab (dMMR/MSI-H and have not used prior ICI)
-adagrasib/sotorasib +/- cetuximab/panitumumab (KRAS G12C)
-entrectinib/larotrectinib (NTRK)
-Selpercatinib (RET)
-others: regorafenib, fruquintinib (RAS/RAF wildtype), or trifluridine/tipiracil (preferred with bevacizumab)
Colorectal cancer secondary preventions
Aspirin - this was rescinded in 2022- (can consider if lynch syndrome)
USPSTF says insufficient evidence, NCCN acknowledges this but still has it in guidelines to consider it
Malignant pleural mesothelioma (asbestos lung cancer)
Epithelioid (best prognosis)
-cisplatin + pemetrexed +/- bevacizumab —> bevacizumab maintenance)
-ipilimumab + nivolumab
Biphasic/Mixed or Sarcomatoid
-ipilimumab + nivolumab (Preffered)
-cisplatin/carbo + pemetrexed +/- (bevacizumab —> bevacizumab maintenance)
Subsequent
-pemetrexed (if not used first line or if good response in first line)
-ipilimumab + nivolumab
Main risk fx is asbestos
-Screening is NOT recommended
-BAP1 is the the mutation we see
-second line switch to what you didn’t give before (ICI vs chemo)
Anal cancer
Localized
-5FU/capecitabine + mitomycin + RT (Nigro protocol)
Locally progressive or recurrent
-abdominoperineal resection (WILL NEED COLOSTOMY)
Metastatic
-carbo + paclitaxel (cat 1)
-cisplatin + 5FU
-FOLFCIS
-FOLFOX
-DCF (doc + cis + 5FU)
Subsequent
-nivo or pembro (regardless of PDL1)
-platinum (if given first line)
Risk fx: hpv, HIV, smoking hx, anal intercourse
Note: may take up to 26 weeks for complete response
Low grade glioma: pilocytic astrocytoma, pilocytic xanthroastrocytoma, ganglioglioma,
These are grade 1
BRAF V600E mutation
-Dabrafenib + trametinib
-vemurafenib + Cobimetinib
BRAF Fusion
-selumetinib
Subependymal giant cell astrocytoma
-everolimus
Adenocarcinoma of the esophagogastric junction
Siewart classification:
Types I-II: Tx as esophageal cancer
Type III: Tx as gastric cancer
I think also you can look at histology and if adenocarcinoma you can treat more like gastric- example: traztuzumab can be used in her-2+ EGJ adenocarcinoma
When to start tx for CLL?
-anemia or thrombocytopenia
-autoimmune cytopenias even after tx with rituximab and high dose steroids
-B- symptoms
-threatened end organ function
-symptomatic lymphadenopathy
-symptomatic extranodal involvement
-lymphocyte doubling time of less than 6 months (maybe)
Even if really high WBC bc we are not worried about leukostasis like with acute leukemias
R/R APL
Early relapse (<6 months) after ATRA + anthracycline, or prior arsenic
-arsenic +/- ATRA +/- Gemtuzumab
Late relapse (>6 months) after arsenic
-Arsenic +/- ATRA +/- anthracycline
Transplant
-auto if MRD negative
-allo if CR but MRD positive
MSI-H/dMMR solid tumors- metastatic or unresectable with no alternatives. Agnostic approvals
Other agnostic approvals for solid tumors unresectable or metastatic with no other options
Pembro (also for TMB >10) or dostarlimab
Nivo +/- in colorectal
Atezolizumab not indicated
Other:
-NTRK
-BRAF V600E: Dabrafenib + trametinib
-RET fusion: Selpercatinib
Chemo regimens for SCLC ABD NSCLC
Limited stage SCLC
-cisplatin + etoposide (+RT)
Extensive stage SCLC
-cisplatin/carboplatin* + etoposide
NSCLC IIA (high risk)-IIIA
-squamous: cisplatin + (gemzar or docetaxel)
-Non- Squamous: cisplatin + pemetrexed
NSCLC neoadjuvant
-any histology: carbo + paclitaxel
-non-squamous: cisplatin + pemetrexed
-squamous: cisplatin + Gemcitabine
NSCLC IIIB
-Non-squamous: cisplatin/carbo + pemetrexed + RT
-All histologies: carbo + paclitaxel + RT
NSCLC Advanced
-Squamous: (paclitaxel, nab-paclitaxel) + cemiplimab/pembro followed by I/O maintenance
-ipilimumab + nivolumab + paclitaxel + platinum —>IPI/nivo
-Non-Squamous: carbo/cis + (pemetrexed, bevacizumab, nab-paclitaxel) + atezolizumab/pembro followed by I/O maintenance
Glioblastoma multi form second line
Lomustine
Double check this
Primary mediastinal lymphoma (PMBL)
-R-EPOCH
-RCHOP (may need RT for residual dx)
R/R:
-pembro
-nivo +/- Brentuximab vedotin
Head and neck secondary prevention
Isotretinoin- can’t do long term d/t toxicity
Head and neck secondary prevention
Isotretinoin- can’t do long term d/t toxicity
Pituitary adenomas (benign)
Bromocriptine - D2 AGONIST, inhibits prolactin release
Note: Cushing’s is a common complication of this tumor
Glioblastomas with EGFR mutations
NCCN doesn’t discuss- ongoing research
Osimertinib has been used after tmz
Recurrent brain tumors
Note: pseudo progression from RT in first 3 months scans look worse
No established second line:
-resection (if able)
-re-irradiation (if able)
-bevacizumab +/- chemo
-TMZ
-nitrosurea (carmustine or lomustine)
-PCV
-regorafenib
-tumor treating fields (alt electric fields)
Chordoma v chondrosarcoma v UPS systemic therapy
Chordoma: imatinib, dasatinib, sunitinib
Chondrosarcoma: dasatinib,
Pazopanib, ivosidenib (IDH mutation)
UPS of bone: osteosarcoma like (AP, MAP)
STS subtypes and first line tx
Uterine leimyosarcoma: Gemcitabine + docetaxel
Myxoid liposarcoma: dox or dox + Dacarbazine
Pleomorphic liposarcoma: dox
Differentiated liposarcoma: dox
Angiosarcoma: dox, Liposomal dox, or paclitaxel
Synovial sarcoma: dox + ifos
Perivascular epithelioid differentiation: nab-sirolimus
Epitheloid sarcoma: tazemetostat
Tenosynovial giant cell tumor/pigmented villonodular synovitis: Pexidartinib
Perivascular epitheloid cell neoplasm (PEComas): nab-sirolimus
Desmoid: observation—> sorafenib
Leimyosarcoma: dox + Dacarbazine
Kaposi sarcoma
Vascular tumor associated with human herpes virus-8 (aka KS herpes virus)
Usually associated with HIV- manage this with ART
Often visible on skin
Limited cutaneous disease
-topicals (imiquimod, alitretinoin)
-intralesional Vinblastine
-RT, local excision, cryotherapy
Advanced disease
-liposomal doxorubicin (preferred)
-sirolimus (transplant Ks)
-paclitaxel
Relapsed/refractory
-pomalidomide (give with ASA)
Avoid steroids- causes flare
Order to consider low risk MDS agents if mx apply
Lenalidomide, luspatercept, epoetin, then Lenalidomide if none apply, then hma
R/R ALL
-if >3 yr can repeat regimen
-FLAG-IDA, FLAM, MOAD, augmented hyper-CVAD, clofarabine based (CLOVE), nelarabine based (NECTAR), inotuzumab, blinatumomab
-CAR-T: tisagenlecleucel (up to 25 y/o), brexucabtagene
-allogenic HCT if you can achieve CR
Treatment of CML during pregnancy
Interferon Alfa
Empiric therapy for cancer of unknown primary
Carboplatin + paclitaxel
Biliary tract /gallbladder
Adjuvant
-capecitabine
Unresectable or metastatic
-Gemcitabine + cisplatin + (Durvalumab or pembrolizumab) (preferred)
-Gemcitabine + cisplatin
Subsequent
-FOLFOX
Targeted
-FGFR inhibitors
Adrenocortical carcinoma
-Surgery
-adjuvant chemo for advanced dx need mitotane +/- (cisplatin/carbo + etoposide)
-unresectable:
-mitotane + EDT (etop, dox, platinum)
-We check mitotane lvls (14-20)
-mitotane can cause aldosterone deficiency
Adrenocortical carcinoma
-Surgery (localized)
-adjuvant chemo for advanced dx need mitotane +/- (cisplatin/carbo + etoposide)
-unresectable:
-mitotane + EDT (etop, dox platinum)
-We check mitotane lvls (14-20)
-mitotane can cause aldosterone deficiency
LCIS Tx
No treatment
We do prevention strategies like surgery or tamoxifen/ AI
No RT
LCIS Tx
No treatment
We do prevention strategies like surgery or tamoxifen/ AI
Breast cancer pregnancy
-chemo in second trimester or post partum
-no RT or ET
-chemo regimens:
-FAC (5FU, dox, cyclo)
Small cell variant of any solid tumor (e.g., small cell prostate cancer)
Think SCLC
Platinum + etoposide +/- IO
Leimyosarcoma first line
Doxorubicin + Dacarbazine
Solitary plasmacytoma
Radiation
Poorly differentiated grade 3 Neuroendocrine carcinomas
Treat like small cell lung cancer
Mitotic rate or ki67 >20
Extraskeletal myxoid chondrosarcoma
Pazopanib
Well differentiated grade 1-2 Neuroendocrine tumors
-Surgery if possible
-somatastatin analongs
-everolimus
-luteum 177 gotatade (mid-gut NET)
-MSI-H, high TMB: pembro
-lots of other crap depending on location
Mitotic rate and ki67 <2
Penile cancer
TIP (paclitaxel, ifosfamide, cisplatin)
Penile cancer
TIP (paclitaxel, ifosfamide, cisplatin)
