Lung Cancer Flashcards
what is the leading cause of death from cancer
lung cance
RF for lung cancer
smoking (↑20x), second hand smoking (↑20-30%), asbestos, hx COPD/ TB/ lupus, immunosuppression, occupational exposure to certain chemicals, exposure to radiation, beta carotene with smoking, outdoor air pollution
S/S of lung cancer
cough, dyspnea, weight loss, chest pain, sx more likely in pts who already have COPD
lung cancer diagnosis requries
CXR, chest CT or PET, bronchoscopy, sputum cytology from cough or bronchoscopy, biopsy via bronchoscopy or fine needle or excisional or from surgery
year for 3 years
lung cancer workup includes
lab tests, consider bone scale, CT/MRI head, CT chest/ abdomen for bone/ brain/ liver/ adrenal metastasis, pulmonary fxn tests
CTFPHC recommends screening with low dose CT every _____in adults who: Are _____yrs, current or former smokers who quit in the last __yrs, min ______ year hx of smoking
every year for 3 years
55-74yrs
15 yrs
30 pack year
lung cancer is divided into 2 histologic types
non small cell lung cancer
small cell lung cancer
prognosis of stage 1 NSCLC
80% 5yr survival
prognosis of stage 4 NSCLC
10% 5yr survival
NSCLC is further divided into
adenocarcinoma (nonsequamous)
squamous cell (epidermoid)
other (large cell)
what is the most common type of NSCLC in nonsmokers
adenocarcinoma (nonsquamous)
what type of cells do adenocarcinomas affect
glandular cells
what type of cells do squamous cell NSCLC affect
squamous cells
treatment for stage 1-3A resectable disease
resection preferred, but pt has to be fit for surgery
+ adjuvant chemo if => stage 2
+ adjuvant radiation or reresecting after adjuvant chemo if + margins
what proportion of pts have nonresectable lung cancer
2/3- includes those who refuse or are unfit for surgery
options for stage 2-3 unresectable disease
concurrent radiation + chemo - if good response on stage 3A = give durvalumab
intense focused radiation, followed by adjuvant chemo
neoadjuvant chemo, surgery, adjuvant radiation
what is a platinum doublet
platinum + other drug
recommendation for stage 1-3A, ECOG 3-4
palliative radiation
cisplatin MOA
covalently binds DNA and disrupts function
cisplatin SEs
ototoxicity, nephrotoxicity, hypokalemia, hypomagnesemia, myelosuppression, N/V
what should be given with cisplatin infusions
K and Mg supplementation + IV fluid
what is dosed based on the carvert formula
carboplatin
what is the benefit of carboplatin over cispatin
less ototoxic and nephrotoxic
what is the downside of carboplatin over cisplatin
more myelosuppressive
what is often used for pts who can’t tolerate cisplatin due to renal insuff?
carboplatin
vinorelbine is a
semisynthetic vinca alkaloid
vinorelbine MOA
inhibits cell growth by binding to tubulin on nitotic MT
vinorelbine SEs
bone marrow suppression
changes in bowel habits (constipation>diarrhea)
sensory neuropathy
alopecia
pemetrexed is an
antifolate antimetabolite
pemetrexed is an antifolate antimetabolite that primarily
inhibits thymidylate synthase which leads to reduced thymidine for DNA synthesis
pemetrexed SEs
bone marrow suppression
diarrhea
mucositis
fatigue
skin rash (less if pretreat with dex)
how to prevent pemetrexed bone marrow suppression, diarrhea, mucositis
folic acid 0.4mg po daily starting 1 wk before first dose + cont 3 wks after last dose
vit B12 1000mcg IM q9wks with first inj 1 wk before first dose, end 3 wks after last dose
gemcitabine MOA
pyrimidine analog whos active metabolites are incorporated into DNA = inhibition of DNA synthesis + induction of apoptosis
gemcitabine AEs
bone marrow suppression
elevated liver enzymes
pulmonary toxicity
durvalumab is indicated in pts that are (3)
stage 3A NSCLC and
have received concurrent chemo + radiation and
has good response to tx (no progression)
durvalumab is an ________ that blocks ________
immune checkpoint inhibitor that blocks PD-L1
how to treat advanced (stage 3B, C) or metastatic lung disease if ECOG 3-4
radiation alone
how to treat advanced (stage 3B, C) or metastatic lung disease if ECOG is 1-2
chemo +/- radiation- platinum doublet
targeted oral therapies - EGFR TKis, ALK TKis, ROS1 TKIs
immune checkpoint inhibitors
Genetic mutations and molecular targets can be identified through _____.
______ can detect presence of PD-L1 in tissues
PCR, FISH, NGS
IHC
NSCLC adenocarcinoma can be further detailed into
EFGR mutation
ALK fusion oncogene
ROS1 rearrangement positive
KRAS mutation
T or F: the overlap between NSCLC is rare
T <3%
common EFGR sensitizing mutations are ______ or _______
deletion exon 19
point mutation exon 21
what is a less common EGFR mutation
T790M
what is true about T790M? select all that apply
1. is a less common EGFR mutation
2. is a common ALK fusion mutation
3. tends to be hereditary
4. tends to be acquired during treatment
1,4
sensitizing EGFR gene mutations are more common in _____ and ______
smokers and females
what are the first gen EGFR TKIs
erlotinib and gefitinib
what is the second gen EGFR TKi
afatinib
what is the third gen EGFR TKi
osimertinib
all EGFR TKis have activity on ______ or ______
exon 19 del or exon 21
what is the only EGFR TKi that has activity on T790M
osimertinib
what EGFR TKi is funded as first line for EGFR sensitizing mutation in alberta
osimertinib
osimertinib benefits
better penetration to brain- passes BBB
only EGFR TKi that targets T790M
AEs for EGFR TKis
fatigue, rash, diarrhea, hepatic dysfunction or increase in liver transaminases, interstitial lung disease
what are 2 ALK fusion oncogene TKis
alactinib and brigatinib
name 3 ALK TKi AEs
GI toxicities - diarrhea (50% with brig), constipation (35% with alect)
N/V (30% with brig)
hepatotoxicity or elevation in transaminases and/or bilirubin
hyperglycemia with brig (initiate appropriate AHG meds)
myalgia with alectinib
symptomatic bradycardia
QTc prolongation
HPTN with brig
CK elevation
ROS1 encodes a _____ and is a _____
Transmembrane receptor
protooncogene
what are 2 ROS TKis
entrectinib and crizotinib
which of the following is true about the KRAS mutation
1. it happens in about 40% of all lung NSCLC adenocarcinoma
2. if it is present, there is likely problems with either EGFR, ALK, ROS1
3. is a good prognostic marker
4. if it is present, EGFR, ALK, ROS1 are unlikely to have mutations too
5. EGFR targets may help
4
entrectinib is a
ROS1 fusion TKi
osimertinib is a
EGFR TKi
which of the following should be taken with or without food
1. osimertinib
2. entrectinib
3. crizotinib
4. alectinib
5. brigatinib
1, 2, 5
which of the following should be taken with food
1. osimertinib
2. entrectinib
3. crizotinib
4. alectinib
5. brigatinib
4
which of the following has pH dependent solubility
1. osimertinib
2. entrectinib
3. crizotinib
4. alectinib
5. brigatinib
2
osimertinib, entrectinib, crizotinib, alectinib, and brigatinib are major CYP ____ substrates
3A4
crizotinib is a TKi for
ROS1
alectinib is a TKi for
ALK
brigatinib is a TKi for
ALK
because erlotinib, gefitinib, osimertinib, entrectnib, crizotinib, alectinib, brigatinib = major CYP3A4 substrate, what should be avoided? what should be monitored?
avoid grapefruit juice
monitor INR for pts on warfarin
what are 4 treatment options for NSCLC nonsquamous with out driver mutations
platinum doublet
ICI monotherapy
platinum doublet with one ICI therapy
platinum doublet with 2 ICI therapies
Regardless of PD-L1 expression levels, immunotherapy is less effective for__________- if there is a driver in metastatic disease, use that as a target first
tumors with driver mutations (EGFR+, ALK+)
if a tumor has high PD-L1 levels and an EGFR mutation, which would be more appropriate therapy
1. osimertanib
2. entrectinib
3. pembrolizumab
4. platinum doublet
5. imilimumab
1- EGFR TKi
always target driver mutations first, before using immunotherapy agents
where are PD-1 receptors present?
activated cytotoxic T cells
where are PD-L1 ligands present
cancer cells
PD-1 inhibit MAbs include
nivolumab, pembrolizumab
PD-L1 inhibitors include
atezolizumab, durvalumab
what is a tumor proportion score?
% of viable tumor cells showing any PD-L1 staining (not the same as somatic genetic mutation)
what is the best for predicting response to pembrolizumab in metastatic NSCLC
PD-L1TPS
the TPS predicts response of metastatic NSCLC to ______
1. pembro
2. nivo
3. atezo
4. durvalu
5. more than one of the above
1
which of the following is true about PD-L1
1. TPS is a measure of the % of tumor cells with PD-L1 staining
2. >50% is a high expression and chooses pembro as second line therapy
3. expression is continuously variable and dynamic, hence cut offs are arbitrary
4. >1% is high expression = pembro is second line therapy
3
if PD-L1 expression is >50% without other driver mutations, what is first line therapy?
pembrolizumab
in order to use immune checkpoint inhibitors like pembrolizumab, pts must have ______
ECOG <2
what is the only PD-1/PD-L1 inhibitor used with a curative intent
durvalumab for stage 3A
pembrolizumab may be combined with __________ for improved 1 yr survival compared to chemo alone
platinum doublet for improved 1yr survival compared to chemo alone
when may pembrolizumab be second line
after progression if the pt did not receive pembro before and PD-L1 =>1
nivolumab is a
PD-1i
nivolumab is used with ______ intent
palliative for advanced/ metastatic
nivolumab is used as first line in combo with
ipilmumab and platinum doublet if no mutations
is PD-L1 score required if nivo is used as first line in combo with ipilumab and platinum coublet?
no
when is nivo indicated as second line tx
after progression on chemo alone
when is atezolizumab used
for palliation after advanced/ metastatic + second line only after rpogression on chemo alone
durvalumab can be used for
curative intent for stage 3A and consolidation (prevent recurrance)
adjuvant- after good response on concurrent chemo + radiation
B7 is present on
dendritic cells
CD28 is on
T cells
CTLA4 is an
immune checkpoint
______ is a CTLA4i
ipilimumab
ipilimumab is synergistic with
PD1 targeting MAbs like nivolumab
data supports the combo of ipilimumab + _______ + ______
nivolumab + chemo
what is a spectrum of SEs caused by general immunologic enhancement
immune mediated AEs
what is considered limited SCLC
cancer contained in single area that can be treated with radiotherapy
can limited SCLC be treated with curative intent?
yes- if pt is fit
what is considered extensive SCLC
cancer has spread to other lung or lymph nodes further away from cancer
distance metastasis present
may be in pleural fluid
extensive SCLC is treat with ____ intent
palliative
SCLC is highly linked to
smokign
which spreads and grows faster? NSCLC or SCLC?
SCLC
SCLC usually starts in cells that
line the bronchi (center of lung)
describe stage 1 SCLC
3.5% pts diagnosed here, 5yr survival of 30%
should you push stage 1 SCLC pts to quit smoking?
yes- 5 yr survival doubles if they stop smoking after dx
describe stage 4 SCLC
67% dx here, 5yr survival 2%, most survive for 7-11mths after
treatment of limited stage SCLC
concurrent chemo + radiation for pts with ECOG 0-1
prophylactic cranial radiation for brain metastasis
treatment of extensive stage SCLC
platinum doublet chemo 4-6 cycles + durvalumab
+ durvalumab maintenance
etoposide is used in lung cancer in
SCLC
