Lung Cancer Flashcards
types of lung cancer
Small Cell (SCLC)
Non-Small Cell (NSCLC)
- Squamous
- Non- Squamous (Large cell carcinoma & Adenocarcinoma)
Signs and symptoms
Pulmonary
- cough
- dyspnea
- chest pain
Extra-pulmonary
- fatigue
- weight loss
- anorexia
Disseminated disease
- Neurologic (CNS metastases)
Paraneoplastic syndromes
- Hypercalcemia and SIADH
SCLC staging
Limited
- confined to 1 lung
- lymph node involvement: same side of chest
Extensive stage
- involves both lungs
- lymph node involvement: both sides of chest
- extra pulmonary metastases
Treatment for Local NSCLC Stage 1
Surgery
Treatment for Local NSCLC Stage 2
Surgery followed by adjuvant therapy
- platinum based reg for 4 cycles
- Osimertinib (EGFR +)
- Atezolizumab (PDL1 >/= 1%)
Neoadjuvant therapy for operable yet difficult to resect tumors
- platinum based reg +/- nivolumab for 4 cycles
Radiation therapy
- reserved for inoperable tumors
- concurrent chemo preferred
Treatment for Local NSCLC Stage 3A
Neoadjuvant chemo +/- nivolumab x4c cycles -> surgery or RT
Adjuvant osimertinib (EGFR+) or atezolizumab (PDL1 > 1)
Concurrent chemoradiotherapy for non-surgical candidates
mTreatment for Local NSCLC Stage 3B-3C
Unresectable disease
concurrent chemoradiation is mainstay
durvalumab maintenance for 1 year upon response to chemoradiotherapy
Cisplatin and Carboplatin ADE
myelosuppression
N/V
diarrhea/constipation
oral mucositis
alopecia
nephrotoxicity
ototoxicity
peripheral neuropathy
Which ADEs occur less with Carboplatin than Cisplatin
N/V
Nephrotoxicity
Ototoxicity
Peripheral neuropathy
Calvert Equation
Total cisplatin dose = AUC x [CrCL + 25]
for calculating CrCL
- ABW < 120% of IBW -> use IBW
- ABW > 120% of IBW -> use ABW
Treatment for Local NSCLC Stage 4 or Relapsed Disease
Targetable genetic mutation (EGFR, ALK, ROS1, BRAF, NTRK, RET, MET)
- kinase inhibitor targeted to mutation
PD-L1 >/= 1%
- PD1/ PDL1 inhibitor +/- chemo
PD-L1 < 1%
- PD1/PDL1 inhibitor AND chemo
EGFR inhibitors
Agents
- first gen: Erlotinib, Gefitinib, Afatinib
- second gen: dacomitinib
- third gen: osimertinib (first line)
Osimertinib
3rd gen EGFR inhibitor
Dose: 80 mg QD
CYP3A4 substrate
no pH dependent absorption
ADE:
- skin rash
- dry skin
- diarrhea
- fatigue
- nail toxicity
- stomatitis
- alopecia
- conjunctivitis
- QTc prolongation
- myelosuppression
ALK inhibitors
First gen: crizotinib, ceritinib
second gen: Alectinib, Brigatinib
Third gen: Lorlatinib
2nd and 3rd gen preferred
Lorlatinib shows improved potency and penetration of BBB
- neurological ADE
Brigatinib
Dose: 90mg QD x 7d, 180 mg QD
QYP3A4 substrate
ADE:
- diarrhea
- fatigue
- pneumonitis
- myalgia
- HTN
Alectinib
Dose: 600 mg BID
CYP3A4 substrate
ADE:
- constipation
- fatigue
- LFT abnormalities
- mood disorders
- myalgia
- HTN
Loratinib
ALK inhibitor
Dose: 100mg
CYP3A4 & P-gp substrate
ADE:
- fatigue
- peripheral edema
- mood disorders
- neuropathy
- cognitive effects
- arthralgia
- dyslipidemia, weight gain
KRAS inhibitors
Indicated for advanced or metastatic NSLCLC and KRAS G12C mutation
AFTER TRIAL OF 1 PRIOR THERAPY
Agents:
- Sotorasib
- Adagrasib
Sotorasib
KRAS inhibitor
CYP3A4 substrate
strong P-gp inhibitor
Avoid PPIs and H2RAs (4h before and 10h after)
ADE:
- diarrhea
- nausea
- fatigue
- LFT abnormalities
- musculoskeletal pain
- dec Hgb/lymphocytes
Adagrasib
KRAS inhibitor
CYP3A4 substrate
moderate inhibitor of P-gp
no pH dependent absorption
ADE:
- diarrhea
- nausea
- fatigue
- LFT abnormalities
- musculoskeletal pain
- dec Hgb / lymphocytes
- renal impairment
- edema
- QT prolongation
- interstitial lung disease / pneumonitis
PDL1 > 50% NSCLC first line treatments
pembrolizumab
atezolizumab
cemiplimab
Squamous PDL1 <50% NSCLC first line
Cis or Carb + Paclitaxel + Pembrolizumab
Cis or Carb + Paclitaxel + Nivolumab + Ipilimumab
Non-squamous PDL1 < 50 NSCLC first line
Cis or Carb + Pemetrexed + Pembrolizumab
Cis or Carb + Pemetrexed + Nivolumab + Ipilimumab
NSCLC 2nd line
No previous checkpoint inhibitor ->
- pembrolizumab
- nivolumab
- atezolizumab
Previous checkpoint inhibitor ->
- Docetaxel + Ramucirumab
- Ramucirumab + Pembrolizumab
- Docetaxel
- Pemetrexed (nonsquamous)
Immunotherapy ADE
Management:
- grade 1: continue immunotherapy
- grade 2: hold immunotherapy and consider corticosteroid
- grade > 3: hold immunotherapy and give corticosteroid
Prednisone 0.5-2 mg/d until grade 1 -> taper over 1 month
ADE:
- encephalitis
- thyroiditis, hypothyroid, hyperthyroid
- mucositis
- pneumonitis
- rash
- thrombocytopenia, anemia
- myocarditis
- hepatitis
- pancreatitis
- adrenal insufficiency
- colitis
- neuropathy
VEGF inhibitors
Agents: Bevacizumab, Ramucirumab
ADE:
- HTN
- thromboembolic events
- epistaxis
- major bleeds
- GI perforation
- proteinuria
- diarrhea (ramucirumab)
avoid in pts with squamous histology (bevacizumab), recent hemoptysis, on therapeutic anticoagulation, recent surgical procedure
Chemo: Taxanes
Agents: paclitaxel, docetaxel
ADE:
- myelosuppression
- alopecia
- peripheral neuropathy
- mucositis
- diarrhea
- N/V
- hypersensitivity rxn (pre-med with dexamethasone, famotidine, diphenhydramine)
- peripheral edema (docetaxel) (pre-med with dexamethasone 8 mg BID day before, day of, and day after)
Chemotherapy: Pemetrexed
Avoid in CrCl < 45
temporary NSAID hold
ADE:
- myelosuppression
- erythematous/pruritic rash
- fatigue
- diarrhea
- N/V
Folic acid and B12 prophylaxis
Dexamethasone 4mg BID day before, of, and after
SCLC
Chemo +/- radiation
1st line:
- Cis + Etoposide
- Carb + Etoposide
- Carb + Etoposide + Atezolizumab (ext stage only)
- Carb + Eto + Durvalumab (ext stage only)
- Cis + Eto + Durvalumab
2nd line:
- Topotecan
- Lurbinectedin
- Clinical trial
Etoposide
Topoisomerase II inhibitor
ADE:
- myelosuppression
- N/V
- stomatitis
- alopecia
Topotecan
Topoisomerase I inhibitor
reduce dose in renal insufficiency
ADE:
- myelosuppression
- diarrhea
- N/V
- fatigue
- alopecia
Lurbinectedin
SCLC chemo agent
ADE
- fatigue
- hepatic enzyme elevation
- extravasation
- nausea
- myelosuppression
- inc SCr
- musculoskeletal pain
Pretreat with dexamethasone (for hepatic enzymes) and 5-HT3 antagonist for N/V
