Lung Cancer Flashcards
What is the MOST likely cause of lung cancer? What other risk factors are there?
TOBACCO SMOKE
Environmental respiratory carcinogens (asbestos, arsenic, air pollution)
Radiation
Genetics
What are some differences between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)?
SCLC: much shorter survival (1-3 MONTHS), rapid tumor growth, rarely surgical interventions but very chemo/RT-sensitive, no target agents
NSCLC: longer survival (1 year), slower tumor growth, surgery routine but not very RT/chemo sensitive, large role for target agents
What are common symptoms of lung cancer?
Pulmonary = dyspnea, cough, chest pain
Red flag = repeat scripts for pneumonia/bronchitis
Fatigue, weight loss/anorexia, hypercalcemia
Metastasis can cause neurologic sx
Superior Vena Cava (SVC) syndrome
Lifetime smoke history is quantified by _____________ how do you calculate this?
“Pack years”
= (years smoking) x (# packs/day)
Who should be screened for lung cancer?
Adults 50-80 yo
Current or former smokers who quit ≤ 15 yrs + ≥ 20 pack-year hx
What is the screening test for lung cancer?
Low Dose CT (LDCT) annually
What are the two steps that need to be taken to diagnose lung cancer?
- CT scan of chest
- Lung tissue biopsy (confirm tumor presence and type)
Define Early Stage, Locally Advanced Stage and Advanced Stage lung cancer
Early: Stage 1 or 2 w/ negative nodes
Locally Advanced: Stage 2 or 3 w/ positive nodes
Advanced: Stage 4
What is the difference between limited stage and extensive stage lung cancer?
Limited: confined to one lung +/- lymph node involvement confined to same side
Extensive: involves both lungs +/- lymph node involvement on both sides +/- extrapulmonary metastases
For EARLY stage NSCLC STAGE 1 what are the steps for resectable vs unresectable cancer?
Resectable: just resection
Unresectable: RT alone
For EARLY stage NSCLC STAGE 2 what are the steps for resectable vs unresectable cancer?
Resectable: +/- neoadjuvant & adjuvant therapy
Unresectable: Concurrent chemo & RT
For EARLY stage NSCLC STAGE 3 what are the steps for resectable vs unresectable cancer?
Resectable: Neoadjuvant therapy, adjuvant therapy, +/- RT
Unresectable: Concurrent chemo+RT, Durvalumab maintenance
What are some neoadjuvant regimens for early stage NSCLC?
Nivolumab + platinum based chemo x 3 cycles
Pembrolizumab + cisplatin chemo x 4 cycles
Platinum based chemo x 4 cycles
What are some adjuvant regimens for early stage NSCLC?
Osimertinib daily ≤ 3 years
Atezolizumab ≤ 1 year
Pembrolizumab ≤ 1 year
Platinum based chemo x 4 cycles
What are the platinum-based chemotherapy regimens? Which are preferred for squamous, nonsquamous and cisplatin-intolerant patients?
Non-squamous:
Cisplatin/pemetrexed
Squamous:
Cisplatin/docetaxel
Cisplatin/gemcitabine
Cisplatin-intolerant:
Carboplatin/pemetrexed
Carboplatin/paclitaxel
Carboplatin/gemcitabine
What are some AEs that CISPLATIN has?
N/V
Diarrhea/constipation
Nephrotoxicity (hypokalemia, Hypomagnesemia)
Ototoxicity
Peripheral neuropathy
What are some AEs that CARBOPLATIN has?
Myelosuppression (thrombocytopenia)
Diarrhea/constipation
(Fewer AEs = better tolerated than cisplatin
What is the weight that should be used for dosing carboplatin?
IBW - standard
Adjusted BW - if actual body weight is 1.2 x IBW
Actual BW - if IBW is less than ABW
What is the equation for IBW?
Male = 50 + (2.3 x inches over 5 foot)
Female 45.5 + (2.3 x inches over 5 foot)
What is the adjusted body weight equation?
IBW + 0.4 x (ABW - IBW)
What is the Cockcroft-Gault equation
(140 - age) x weight kg
——————————- x 0.85 if female
72 x SCr
What is the equation for carboplatin dosing? What is the max CrCl used?
Target AUC x (CrCl + 25)
CrCl ≤ 125 mL/min
What are some major AEs of the taxanes (paclitaxel/docetaxel)?
Alopecia
Peripheral neuropathy
Hypersensitivity reaction (premeditate, from the solvent)
Peripheral edema (docetaxel only)
How is Pemetrexed eliminated? What level should it be avoided in?
Renal elimination
Avoid use if CrCl < 45
What are some AEs of Pemetrexed? What should it be supplemented with??
Red/pruritic skin rash
Diarrhea
Fatigue
Supplement with: Folic acid + Vitamin B12
- use dexamethasone BID the days around chemo to decrease rash incidence
For advanced NSCLC, we primarily use targetable genetic mutation therapy. Which mutations do we target?
EGFR (epidermal growth factor receptor)
ALK
KRAS
(ROS-I, BRAF, NTRK, MET, RET, HER-2)
EGFR mutations are most prevalent in _______ and ________ in lung cancer. They target exon ____ deletions and exon ____ mutations
Most prevalent in adenocarcinomas and non-smokers
Target exon 19 deletion and exon 21 point mutations
What are some EGFR drugs used in advanced NSCLC? Which is first line?
1st gen: erlotinib, gefitinib, afatinib
2nd gen: dacomitinib
3rd gen: Osimertinib (1st line)
-improved CNS activity and tolerability
What are some AEs of of EGFR inhibitor Osimertinib?
Skin rash
Dry skin
Conjunctivitis
Diarrhea
Fatigue
Nail Toxicity
Stomatitis
Myelosuppression
QTc prolongation
What are some nonpharmacologic PREVENTION strategies for EGFR inhibitor-related rash? What are some TREATMENTS?
Prevention = sun screen, gentle skin care (loose clothes, avoid hot showers, avoid OTC acne products, use hydrophilic creams)
Rx = topical or systemic corticosteroids/antibiotics
ALK inhibitor drugs for advanced NSCLC are all _____ drugs
Oral
Of the ALK inhibitor drugs for advanced NSCLC, why are Alectinib and Lorlatinib preferred?
Alectinib = only ALK inhibitor with significant improvement in survival
Lorlatinib = 3rd gen, improved potency and BBB penetration
Only 2nd and 3rd gen ALK inhibitors are used in practice for NSCLC. Name these drugs!
2nd gen = Alectinib, brigatinib
3rd gen = Lorlatinib
What are some AEs of ALK inhibitor brigatinib?
Interstitial lung disease
HTN
Diarrhea
Myalgia
What are some AEs of ALK inhibitor Alectinib?
LFT abnormalities
Anemia
Constipation
Myalgia
What are some AEs of ALK inhibitor Lorlatinib?
Higher BBB penetration = more CNS AEs
**Mood disorders
Neuropathy
Cognitive effects
Dyslipidemia & weight increase**
KRAS inhibitors used for advanced NSCLC is most common in ________ patients and confer a _____ prognosis
Common in SMOKERS
Has POOR prognosis
Name the two KRAS inhibitors used in NSCLC.
Sotorasib
Adagrasib
“-rasib”
What is a special consideration with KRAS inhibitor sotorasib?
Requires an acidic environment for proper oral bioavailability
Avoid PPIs or H2RAs
Classifying treatments for advanced NSCLC is dependent on PD-LI positive (PD-LI 1-49%, >50%) or negative (PD-LI <1%) status. What is the regimen for pts w PD-LI 1-49%? >50%? What is the regimen for negative pts?
POSITIVE:
PD-LI > 50% = PD-I/PD-LI inhibitor only
PD-LI 1-49% = PD-I/PD-LI inhibitor + chemo
NEGATIVE:
PD-I/PD-LI inhibitor + chemo
What are some immunotherapy agents that can be used to treat PD-LI in advanced NSCLC?
Pembrolizumab, Cemiplimab (can be be used with chemo)
Atezolizumab
If a lung cancer patient has disease progression even with therapy (NON-CHECKPOINT) what should they try?
Pembrolizumab
Nivolumab
Atezolizumab
If a lung cancer patient has disease progression even with therapy (PRIOR CHECKPOINT) what should they try?
Docetaxel + Ramucirumab (preferred over single agent)
Docetaxel
Gemcitabine
Albumin-Bound Paclitaxel
Pemetrexed (if nonsquamous)
What is the MOA of PD-L1? Aka why are PD-L1 inhibitors effective?
PD-L1 makes T-cells recognize the cancer cells as normal/prevents it from attacking. PD-L1 inhibitors cover the site from recognition and allow the T cell to attack and recruit the immune system.
What are the grades of immunotherapy-related AEs? (Similar to exam 1) describe what actions should be taken for each grade
Caution in autoimmune disorder pts!
Grade 1 = continue immunotherapy
Grade 2 = hold therapy and consider corticosteroid
Grade 3+ = 0.5-2 mg/kg/day x 1 month prednisone until grade 1
What is VEGF MOA and why is it crucial to inhibit?
VEGF is an angiogenic factor that is secreted by cancer cells to create new vessels. By inhibiting VEGF, we cut off nutrition to the cancer
What are the two VEGF inhibitors used in NSCLC?
Bevacizumab
Ramucirumab
What are acute AEs of VEGF inhibitors? What are some delayed AEs?
Acute: HTN
Delayed: [deals w bleeding] thrombosis, epistaxis, major bleeding, GI tears, proteinuria, diarrhea (ramcirumab)
In what type of pts should we avoid use of VEGF inhibitors?
Squamous histology (bevacizumab)
Recent hemoptysis [blood from mouth]
On anticoag therapy for VTE
Recent surgery
(Aka any recent risk for bleeding)
In SCLC, how quick is relapse after complete drug response? What kind of radiation is offered after partial/complete drug response?
Relapse usually 6-8 months after complete response
Prophylactic cranial radiation 🧠 is offered post-response
What chemo/RT is offered FIRST LINE in limited stage SCLC?
Cisplatin + Etoposide + RT
Carboplatin + Etoposide + RT
What chemo/RT is offered FIRST LINE in extensive stage SCLC?
Carboplatin + Etoposide + Atezolizumab (immunotherapy)
Carboplatin + Etoposide + Durvalumab
Cisplatin + Etoposide + Durvalumab
What chemo/RT is offered SECOND LINE in SCLC?
Topotecan
Lurbinectedin
What is the MOA of Etoposide (SCLC)? What is a notable AE?
MOA - topoisomerase II inhibitor, DNA double strand breaks
AE - myelosuppression
What is the MOA of topotecan (SCLC)? What are some notable AEs?
Topoisomerase I inhibitor, leads to DNA single strand breaks
AEs - Myelosuppression, neutropenia
What is the MOA of Lurbinectedin (SCLC)? What are some notable AEs? What should be used for pretreatment?
MOA - alkylates DNA residues and results in DNA damage
AEs - Fatigue, hepatic enzyme elevation, nausea, extravasation (leakage of blood)
Pretreat w dexamethasone (decrease hepatic elevations) and 5-HT3 antagonists for antiemetic
