Exam 2 lecture 4 (Lung) Flashcards
Risk factors for lung cancer?
tobacco (85-90% of cases), risk decreases after cessation, but never to baseline.
occupational/environmental exposure to asbestos
ionizing radiation (2nd leading cause)
Genetic predisposition
What do EGFR mutations mean in lung cancer? What percent of NSCLC is it present in? Which mutation causes it to be resistant to therapies?
What do K-RAS mutations predict? what are these mutations exclusive towards in adeno carcinomas?
EGFR mutations can predict sensitivity to tyrosine kinase inhibitor therapy. Present in 10-15% of NSCLC. T790 mutations cause resistance to therapies.
K-RAS mutations predict resistance to TKI’s. In adenocarcinomas, mutations are exclusive to smokers,
What are the different types of NSCLC? Where are they located in the lung? Are they related to smokers or non smokers.
1) Adenocarcinoma (50%)- most common in non smokers, located peripherally in lung
2) Squamous (30%)- Clearly related to smoking, located centrally
3) large cell (5%)- tend to be located peripherally
4) non-squamous
What percent of cancer is SCLC? Is it related to smoking? How fast does it grow? Symptoms?
15%
Related to smoking
Fast growing and rapidly progressive
paraneoplastic syndromes
compare SCLC and NSCLC
SCLC is highly sensitive to radiation and chemo, NSCLC is moderately sensitive to radiation and marginally sensitive to chemo.
NSCLC has slower growth fraction.
SCLC has clear relationship to smoking and has paraneoplastic syndromes
How fast do SCLC and NSCLC proliferate? What percent metastasize?
SCLC has rapid proliferation, 2/3rds present with metastases
NSCLC is slower growing and 50% present with metastases
What are the staging of SCLC and their 5-year survival
Limited stage- tumor is confined in hemothorax and contained in radiation port (20% chance if survival)
Extensive stage- tumlr is not confined to hemithorax of origin, not contained in radiation port, distant metastasis (5% chance of survival)
use of prophylactic cranial radiation in SCLC when pt obtains complete response
more than 50% of pts will develop brain metastases. SO it increases survival
How to treat limited stage disease SCLC
Highly sensitive to radiation so will be given concurrently with cisplatin and etoposide.
how to treat extensive stage for SCLC
platinum based combination chemo without radiation preferred.
prophylactic cranial radiation should be strongly considered if a patient achieves a response in the chest
what to do if brain metastases are present i extensive stage SCLC
brain radiation therapy
If patient is symptomatic, whole brain radiation should be started prior to chemotherapy.
if asymptomatic, initiate radiation therapy after chemo
What are the 1st line regimens for extensive stage SCLC
Carboplatin + etoposide + Atezolizumab
Durvalumab + Carboplatin + etoposide
Cisplatin + Etoposide + Durvalumab
complications of SCLC therapy
most cisplatin based regimens causes serious ototoxicity and nephro toxicity and neuropathy
which platin causes more myelosuppression cisplatin or carboplatin
Carboplatin
what is an option for metastatic SCLC in patients who have progressed on or after platinum based chemo and atleast one prior line of therapy
PD- inhibitor- pembrolizumab
how sensitive is NSCLC to radiation and chemo? What is the most efficacious treatment of NSCLC? What do we use if this is not available?
moderately sensitive to radiation and low sensitivity to chemo
surgery is most efficacious for NSCLC
radiation therapy may be given for early stage NSCLC when surgery is not viable
what are the three types of NSCLC
Resectable
unresectable
advanced/metastatic
steps for resectable NSCLC
neoadjuvant
surgery
chemo followed by immunotherapy or oral agent
how to decide which neoadjuvant to use for resectable NSCLC
based on histology (squamous vs non squamous)
Non squamous NSCLC adjuvant therapy options
Cisplatin + pemetrexed
Preferred squamous adjuvant therapy options? What if they dont tolerate cisplatin?
cisplatin + gemcitabine
cisplatin + docetaxek
other recommended regimens- cisplatin + vinorelbine
cisplatin + etoposide
if not able to tolerate cisplatin- Carboplatin + Pacitaxel
carboplatin + gemcitabine
What are additional adjuvant therapies used in ALK mutations? eGFR mutations (exon 19 deletion, exon 21 L858R)? PDL-1>1%?
- ALK mutation positive- alectinib
- positive for EGFR mutations (exon 19, exon 21 deletion L858R)- osimertinib
- PD-L1 >1%- Atezolizumab
treatment of unresectable NSCLC
chemo and radiation
stage III unresectable treatement for patients that can not get definitive chemo with radiation
pembrolizumab
what drug can we give for unresectable stage III NSCLC with disease that has not progressed following concurrent chemotherapy and radiation therapy
durvalumab
optimal regimen for stage IIIB and IV disease NSCLC unresectable
cisplatin/paclitaxel
cisplatin/ gemcitabine
Cisplatin/ docetaxel
carboplatin/paclitaxel
absolutely no difference in survival among groups
carboplatin/paclitaxel had fewer toxicities
treatment of advanced/metastatic NSCLC
chemotherapy targeted therapy (1st line)
Chemotherapy targeted therapy (2nd line)
If a patient has a targetable mutation and is PD-L1 (+) for advanced/metastatic adenocarcinoma lung cancers what do we use
It is preferred to use the oral therapies first and then move on to immuno therapies later
What are the most common EGFR mutations in advanced/metastatic unresectable NSCLC? How to treat them? What percent of adeno carcinomas is it present in?
exon 19 deletion and exon 21 L858R mutation
Osimertinib is 1st line if T790 mutation is present
present in 10-15% of adenocarcinomas
WHat drugs are used in non resectable advanced/metastatic NSCLC in BRAF mutations? Side effects associated with these drugs?
Dabrafenib plus trametinib
dabrafenib- fevers, secondary skin cancers
trametinib- fevers, rash, visual changes retinal detachment
What are K-RAS mutations associated with in unresectable advanced/metastatic NSCLC? When are KRAS inhibitors used? What drug is it?
Associated with cigarette smoking
use as subsequent therapy after platinum based chemotherapy
sotorasib is drug name
What to do for metastatic NSCLC unresectable if no mutation or if targeted oral chemo options have been exhausted
Check PD-L1 status. PD-L1 positivity of >1% will allow use of pembrolizumab
treatment of mutation positive metastatic NSCLC non squamous
Oral chemo
|
PD-L1 status 1-49%= pembrolizumab (preferred)
Also look at PS to determine if single agent or pembrolizuman + chemo is best for patient
PD-L1 status >50%-
1. pembrolizumab or pembrolizumab + chemo
2. atezolizumab or
4. cemiplimab- rwlc +/- chemo
PD=L1 negative- a) pembrolizumab or atezolizumab + chemo (preferred)
b) platinum based chemo alone if immunotherapy is contraindicated
first line tx for metastatic mutation negative NSCLC non squamous
Carboplatin + pemetrexed + pembrolizumab
treatment of metastatic NSCLC squamous
if no contraindication to immunotherapy
1. pembrolizumab
2. pembrolizumab + cehmo
3. Atezolizumab or nivolumab or cemiplimab- rwlc
if contraindication to immunotherapy
Platinum doublet regardless of PD-L1 status
first line for squamous metastatic NSCLC
platinum based doublet has been standard ( carboplatn with paclitaxel)
pembrolizumab + carboplatin + paclitaxel or albumin bound paclitaxel
