Lecture 13 - Lung Cancer Flashcards
Lung cancer is the ____ most common
2nd
#1 killer
survival rates have greatly improved
Risk factors
tobacco, occupational/environmental exposure to asbestos, heavy metals, radon, polycyclic aromatic hydrocarbons, ionizing radiation, genetic predisposition
Etiology
chronic exposure of epithelial cells to carcinogens results in chronic inflammation; induces genetic and cytologic changes which eventually lead to carcinogenesis
Etiology - EGFR mutations
can predict sensitivity to tyrosine kinase inhibitor therapy
T790M mutations: resistance to therapies (osimertinib is drug for this mutation)
Etiology - K-RAS mutations
predict resistance to TKIs
in adenocarcinomas, mutations are exclusive to smokers
Etiology - ALK inhibition
less sensitive to EGFR inhibitors and chemo
present in no/light smokers, young age, adenocarcinoma
Etiology - ROS-1 mutations
encodes a receptor kinase related to ALK
present in never/light smoker, young pts, adenocarcinomas
Etiology - BRAF V600E
in current/former smokers
recommended to rest in 1st line metastatic setting for NSCLC
Etiology - PD-L1 status
recommended to test status in 1st line metastatic setting
Histologic classification
non-small cell (NSCLC): adenocarcinoma (non-smokers), squamous (smokers), large cell, and non-squamous
small cell (SCLC): small cell (related to smoking)
Small cell lung cancer
clear relationship to smoking
paraneoplastic syndromes common
rapid cell growth fraction
highly sensitive to radiation and chemo
most common cancer to cause brain metastases
Non-small cell lung cancer
slower growth fraction
moderately sensitive to radiation
marginal sensitivity to chemo
Staging: SCLC
limited: tumor confined to hemithorax and contained in radiation port
extensive stage: tumor not confined to hemithorax of origin, not contained in radiation port, distant metastasis
Small cell lung cancer highly sensitive to
radiation and chemo
chemo demonstrates 5-fold increase in median survival and is the mainstay of therapy
surgery is generally not a therapeutic option
Limited stage disease
curative intent
combined modality: radiation + combo chemo - cisplatin + etoposide, radiation daily
maintenance chemo is of no value
prophylactic cranial radiation for pts obtaining a complete response
Regimens for limited stage
cisplatin + etoposide
carboplatin + etoposide
Extensive state
NO radiation!
rarely curable
platinum based combo chemo w/o radiation preferred: cisplatin or carbolatin based combo chemo - etoposide or irinotecan
chest radiation does not improve results
whole brain radiation therapy if brain metastases present
maintenance chemo is standard of care
Immunotherapy: extensive stage
first line: atezolizumab + carboplatin + etoposide; durvalumab + carboplatin + etoposide; durvalumab + cisplatin + etoposide
Complications of therapy for SCLC
most cisplatin-based regimens: serious chemo induced N/V, nephrotoxicity, ototoxicity, neuropathy
radiation therapy may cause fatigue, esophagitis, radiation pneumonitis, and cardiac toxicity
PD-1 inhibitors
pembrolizumab: option for metastatic SCLC in pts who have progressed on or after platinum-based chemo and at least 1 prior line of therapy
regardless of PD-1 status
Non-small cell lung cancer
moderately sensitive to radiation and low sensitivity to chemo
surgery is most efficacious!
radiation therapy may be given for early-stage NSCLC when surgery isn’t able to be performed
Types of NSCLC
resectable
unresectable
advanced/metastatic
Treatment of resectable NSCLC
neoadjuvant –> surgery –> chemo followed by immunotherapy or oral agent
Neoadjuvant therapy NSCLC
nivolumab + a platinum doublet in tumors >/= 4 cm or node +
adjuvant chemo now a standard of care; chemo decided on histology
Adjuvant therapy for non-squamous NSCLC
cisplatin + premetrexed
Adjuvant therapy for squamous NSCLC
cisplatin + gemcitabine
cisplatin + docetaxel
other recommended regimens: cisplatin + vinorelbine, cisplatin + etoposide
if not able to tolerate cisplatin: carboplatin + pacitaxel or gemcitabine
Additional adjuvant therapies
alectinib: early stage and + for ALK mutations
osimertinib: early stage, + for EGFR mutations (exon 19 deletion, exon 21 L858R)
atezolizumab: early stage, high risk, PD-L1 >/=1% and no mutations
pembrolizumab: early stage, high risk, and no mutations
Treatment of unresectable NSCLC
chemo and radiation
NO surgery!
Unresectable disease: stage IIIB/IV
treatment is palliative, not curative
concurrent chemoradiation: if non-squamous: carboplatin + premetrexed, cisplating + premetrexed, placlitaxel + carboplatin, cisplatin + etoposide if squamous: paclitaxel + carboplatin, cisplatin + etoposide
if no disease progression after definitive concurrent chemoradiation: durvalumab or osimertinib
Stage III unresectable: immunotherapy
pembrolizumab - for pts who aren’t candidates for surgery or definitive chemo with radiation
PD-L1 >/= 1%
Unresectable stage III immunotherapy maintenance
durvalumab: for disease that has not progressed following concurrent chemo and radiation therapy
max of 12 mo of therapy
Stage IIIB and IV disease
optimal regimen not defined: cisplatin/paclitaxel; cisplatin/gemcitabine; cisplatin/docetaxel; carboplatin/paclitaxel (fewer toxicities)
Advanced/metastatic NSCLC treatment
chemo + targeted therapy (1st line)
chemo + targeted therapy (2nd line)
Metastatic NSCLC treatment considerations
adenocarcinoma –> target or no target
squamous
other
check mutation status for all advanced/metastatic adenocarcinoma lung cancers
Tyrosine kinase inhibitors
if pt has targetable mutation and PD-L1 (+), it is preferred to use oral therapies 1st and then move to immunotherapy later
Metastatic NSCLC adenocarcinoma - EGFR targeting therapies
most common mutations: exon 19 deletion and exon 21 L858R mutation
osimertinib - 1st line (T790 mutation)
CYP3A4; rash, diarrhea, cardiomyopathy, QTc prolongation
Metastatic NSCLC adenocarcinoma - BRAF therapies
dabrafenib + trametinib
2 diff pathways; BRAF inhibitor SE –> skin cancer, use trametinib to take risk away
dabrafenib: CYP3A4, fevers, secondary skin cancers
trametinib: fevers, rash, visual changes, retinal detachment
Metastatic NSCLC adenocarcinoma - K-RAS G12C mutation
associated with cigarette smoking
use as subsequent therapy after platinum-based chemo +/- immunotherapy
sotorasib: N/V, diarrhea, increase in LFTs, rash, edema, decreased hemoglobin
Treatment - Metastatic disease - no mutation
if no mutation: check PD-L1 status - if PD-L1 positivity of >/= 1% will allow use of pembrolizumab therapy
if PD-L1 negative: pembrolizumab or atezolizumab + chemo
Metastatic disease - first line: non-squamous
mutation negative NSCLC: carboplatin + pemetrexed + pembrolizumab
Treatment metastatic: squamous
if contraindication to immunotherapy: platinum doublet regardless of PD-L1 status
if no contraindication to immunotherapy: pembrolizumab or pembrolizumab + chemo or atezolizumab
First line metastatic squamous
platinum based doublet
carboplatin combined with gemcitabine or paclitaxel or nab-paclitaxel or docetaxel
new standard with 3 drug regimen: pembrolizumab + carboplatin + paclitaxel or albumin bound paclitaxel
Next line of therapy for metastatic squamous
tyrosine kinase inhibitor (if positive)
immunotherapy or non-platinum chemo
agents: nivolumab, atezolizumab, or pembrolizumab
other single agents: pemetrexed, paclitaxel, docetaxel, gemcitabine, vinorelbine
Immunotherapy toxicities
safety: rare and serious immune mediated toxicities: pneumonitis, colitis, hepatitis, nephritis, endocrine - thyroid, pituitary
Lab values to monitor in pts receiving immunotherapy
amylase, lipase, TSH, free T4, CBC with differential, complete metabolic panel
Lung cancer screening
sputum cytology, serial chest X-rays of no proven benefit
low dose CT scans decreased mortality by 20% - lots of false positives
can consider screening in pts considered to be high-risk
Lung cancer prevention trials
CARET trial: 28% increase of lung cancer with beta carotene
smoking cessation decreased risk of 2nd cancers
What would be the preferred treatment regimen for someone with limited stage SCLC?
radiation + combination chemo: cisplatin + etoposide, radiation daily
no maintenance therapy
What would be the preferred treatment regimen for someone with extensive stage SCLC?
atezolizumab + carboplatin + etoposide
chemo followed by maintenance atezolizumab
OR durvalumab + carboplatin + etoposide
chemo followed by durvalumab maintenance therapy
What would be the preferred regimen for someone with stage II, NSCLC with no mutations?
stage II = resectable
surgery, adjuvant therapies
