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PHRM 864 > Lecture 13 - Lung Cancer > Flashcards

Lecture 13 - Lung Cancer Flashcards

1
Q

Lung cancer is the ____ most common

A

2nd
#1 killer
survival rates have greatly improved

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2
Q

Risk factors

A

tobacco, occupational/environmental exposure to asbestos, heavy metals, radon, polycyclic aromatic hydrocarbons, ionizing radiation, genetic predisposition

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3
Q

Etiology

A

chronic exposure of epithelial cells to carcinogens results in chronic inflammation; induces genetic and cytologic changes which eventually lead to carcinogenesis

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4
Q

Etiology - EGFR mutations

A

can predict sensitivity to tyrosine kinase inhibitor therapy
T790M mutations: resistance to therapies (osimertinib is drug for this mutation)

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5
Q

Etiology - K-RAS mutations

A

predict resistance to TKIs
in adenocarcinomas, mutations are exclusive to smokers

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6
Q

Etiology - ALK inhibition

A

less sensitive to EGFR inhibitors and chemo
present in no/light smokers, young age, adenocarcinoma

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7
Q

Etiology - ROS-1 mutations

A

encodes a receptor kinase related to ALK
present in never/light smoker, young pts, adenocarcinomas

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8
Q

Etiology - BRAF V600E

A

in current/former smokers
recommended to rest in 1st line metastatic setting for NSCLC

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9
Q

Etiology - PD-L1 status

A

recommended to test status in 1st line metastatic setting

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10
Q

Histologic classification

A

non-small cell (NSCLC): adenocarcinoma (non-smokers), squamous (smokers), large cell, and non-squamous
small cell (SCLC): small cell (related to smoking)

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11
Q

Small cell lung cancer

A

clear relationship to smoking
paraneoplastic syndromes common
rapid cell growth fraction
highly sensitive to radiation and chemo
most common cancer to cause brain metastases

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12
Q

Non-small cell lung cancer

A

slower growth fraction
moderately sensitive to radiation
marginal sensitivity to chemo

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13
Q

Staging: SCLC

A

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

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14
Q

Small cell lung cancer highly sensitive to

A

radiation and chemo
chemo demonstrates 5-fold increase in median survival and is the mainstay of therapy
surgery is generally not a therapeutic option

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15
Q

Limited stage disease

A

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

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16
Q

Regimens for limited stage

A

cisplatin + etoposide
carboplatin + etoposide

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17
Q

Extensive state

A

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

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18
Q

Immunotherapy: extensive stage

A

first line: atezolizumab + carboplatin + etoposide; durvalumab + carboplatin + etoposide; durvalumab + cisplatin + etoposide

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19
Q

Complications of therapy for SCLC

A

most cisplatin-based regimens: serious chemo induced N/V, nephrotoxicity, ototoxicity, neuropathy
radiation therapy may cause fatigue, esophagitis, radiation pneumonitis, and cardiac toxicity

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20
Q

PD-1 inhibitors

A

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

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21
Q

Non-small cell lung cancer

A

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

22
Q

Types of NSCLC

A

resectable
unresectable
advanced/metastatic

23
Q

Treatment of resectable NSCLC

A

neoadjuvant –> surgery –> chemo followed by immunotherapy or oral agent

24
Q

Neoadjuvant therapy NSCLC

A

nivolumab + a platinum doublet in tumors >/= 4 cm or node +
adjuvant chemo now a standard of care; chemo decided on histology

25
Q

Adjuvant therapy for non-squamous NSCLC

A

cisplatin + premetrexed

26
Q

Adjuvant therapy for squamous NSCLC

A

cisplatin + gemcitabine
cisplatin + docetaxel
other recommended regimens: cisplatin + vinorelbine, cisplatin + etoposide
if not able to tolerate cisplatin: carboplatin + pacitaxel or gemcitabine

27
Q

Additional adjuvant therapies

A

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

28
Q

Treatment of unresectable NSCLC

A

chemo and radiation
NO surgery!

29
Q

Unresectable disease: stage IIIB/IV

A

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

30
Q

Stage III unresectable: immunotherapy

A

pembrolizumab - for pts who aren’t candidates for surgery or definitive chemo with radiation
PD-L1 >/= 1%

31
Q

Unresectable stage III immunotherapy maintenance

A

durvalumab: for disease that has not progressed following concurrent chemo and radiation therapy
max of 12 mo of therapy

32
Q

Stage IIIB and IV disease

A

optimal regimen not defined: cisplatin/paclitaxel; cisplatin/gemcitabine; cisplatin/docetaxel; carboplatin/paclitaxel (fewer toxicities)

33
Q

Advanced/metastatic NSCLC treatment

A

chemo + targeted therapy (1st line)
chemo + targeted therapy (2nd line)

34
Q

Metastatic NSCLC treatment considerations

A

adenocarcinoma –> target or no target
squamous
other
check mutation status for all advanced/metastatic adenocarcinoma lung cancers

35
Q

Tyrosine kinase inhibitors

A

if pt has targetable mutation and PD-L1 (+), it is preferred to use oral therapies 1st and then move to immunotherapy later

36
Q

Metastatic NSCLC adenocarcinoma - EGFR targeting therapies

A

most common mutations: exon 19 deletion and exon 21 L858R mutation
osimertinib - 1st line (T790 mutation)
CYP3A4; rash, diarrhea, cardiomyopathy, QTc prolongation

37
Q

Metastatic NSCLC adenocarcinoma - BRAF therapies

A

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

38
Q

Metastatic NSCLC adenocarcinoma - K-RAS G12C mutation

A

associated with cigarette smoking
use as subsequent therapy after platinum-based chemo +/- immunotherapy
sotorasib: N/V, diarrhea, increase in LFTs, rash, edema, decreased hemoglobin

39
Q

Treatment - Metastatic disease - no mutation

A

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

40
Q

Metastatic disease - first line: non-squamous

A

mutation negative NSCLC: carboplatin + pemetrexed + pembrolizumab

41
Q

Treatment metastatic: squamous

A

if contraindication to immunotherapy: platinum doublet regardless of PD-L1 status
if no contraindication to immunotherapy: pembrolizumab or pembrolizumab + chemo or atezolizumab

42
Q

First line metastatic squamous

A

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

43
Q

Next line of therapy for metastatic squamous

A

tyrosine kinase inhibitor (if positive)
immunotherapy or non-platinum chemo
agents: nivolumab, atezolizumab, or pembrolizumab
other single agents: pemetrexed, paclitaxel, docetaxel, gemcitabine, vinorelbine

44
Q

Immunotherapy toxicities

A

safety: rare and serious immune mediated toxicities: pneumonitis, colitis, hepatitis, nephritis, endocrine - thyroid, pituitary

45
Q

Lab values to monitor in pts receiving immunotherapy

A

amylase, lipase, TSH, free T4, CBC with differential, complete metabolic panel

46
Q

Lung cancer screening

A

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

47
Q

Lung cancer prevention trials

A

CARET trial: 28% increase of lung cancer with beta carotene
smoking cessation decreased risk of 2nd cancers

48
Q

What would be the preferred treatment regimen for someone with limited stage SCLC?

A

radiation + combination chemo: cisplatin + etoposide, radiation daily
no maintenance therapy

49
Q

What would be the preferred treatment regimen for someone with extensive stage SCLC?

A

atezolizumab + carboplatin + etoposide
chemo followed by maintenance atezolizumab
OR durvalumab + carboplatin + etoposide
chemo followed by durvalumab maintenance therapy

50
Q

What would be the preferred regimen for someone with stage II, NSCLC with no mutations?

A

stage II = resectable
surgery, adjuvant therapies

PHRM 864 (20 decks)

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