Lung Cancer EXAM 3 Flashcards
What are the 3 mechanisms that cause abnormal cell proliferation/differentiation in lung cancer?
- Protooncogene acitvation
- Tumor suppressor gene inactivation
- Immune system evasion (PD-L1 expression)
Which Protoonco genes are commonly upregulated in lung cancer?
EGFR (NSCLC), KIT (SCLC)
-EGFR, ALK, BRAF, MET, RET, ROS1 mutations
What is the most common cause of lung cancer?
Smoking (80% of lung cancer deaths)
What are the secondary causes of lung cancer?
secondhand smoke
asbestos
radon (old houses)
What are common symptoms of a patient with lung cancer?
-Hemoptysis (coughing up blood)
-Cough, hoarseness !!! (most common)
-Dyspnea
-Blood-tinged or purulent sputum
-Chest, shoulder, or arm pain
-Wheezing, stridor
-Superior vena cava syndrome
-Dysphagia
-Pleural effusion, pneumonitis
Which test is used to screen for lung cancer? How often should it be performed?
low-dose CT scan
-done 3x yearly
Which patient population is screened for lung cancer?
Adults 55-80 yoa who have 30year-pack history, and have smoked for at least the last 15 years
(if they have quit for 16 or more years they don’t qualify for screening)
Which lung cancer type grows rapidly and which slowly?
rapidly: small-cell -> SMOKER
slowly: non-small-cell (80% of lung cancer)
-squamous -> SMOKER
-adenocarcinoma
-large cell
Which anticancer drug has lower efficacy in squamous cell lung cancer? Why?
Pemetrexed
squamous cell cancer has higher levels of Thymidylate synthetase enzymes (TS) -> greater resistance to the drug
Why does histology (checking lung tissue) matter in lung cancer treatment?
to differentiate between squamous and adenocarcinoma
for squamous we don’t use pemetrexed bc of high expression of TS
Which genetic mutations are associated with adenocarcinoma patients who are non-smokers?
-EGFR
-BRAF V600E
-ALK
-ROS1
-MET
-RET
-KRASG12C
What are the most important chemotherapy drugs for NSCLC and SCLC?
Cisplatin or Carboplatin + another chemotherapy drug + immunocheckpoint inhibitor
may use immune checkpoint inhibitor alone if PD-L1 is high
EGFR antagonists (especially TKIs) work well with which type of mutations?
EGFR (always ON) activating mutation
-Exon 19 deletion
-Exon 21 L858R mutation
Drugs: TKIs (-inib)
-Erlotinib
-afatinib
-gefitinib
-osimertinib (Tagrisso) !!!
What is the unique toxicity of EGFR antagonists?
-Rash
-Diarrhea
Which TKI has lower rates of diarrhea?
Osimertinib
bc it has a higher affinity for mutated EGFR and doesn’t affect healthy cells as much
What is the brand name of Osimertinib?
Tagrisso
What are the 4 major counseling points for patients with an acne-like rash after lung cancer treatment?
-use non-irritating soap (no astringent or EtOH)
-avoid sun exposure, use sunscreen
-use non-irritating moisturizers
-refer to the doctor for severe lesions
What are the treatment options for severe acne lesions?
topical corticosteroids
doxycycline
What are the unique toxicities of immune checkpoint inhibitors (PD-1 monoclonal antibodies)?
Nivolumab and pembrolizumab
Immune-mediated: LEGS
Liver (increase in AST/ALT and bilirubin)
Endocrine (pituitary, thyroid, adrenal)
GI (diarrhea, colitis)
Skin (rash, dermatitis, vitiligo-killing of melanocytes)
also cardiac (myocarditis, pericarditis)
-treat with corticosteroids
How are toxicities of immune checkpoints treated?
Nivolumab and pembrolizumab
corticosteroids: 1-2 mg/kg prednisone equivalent daily until symptoms improve
-adrenal insufficiency: hydrocortisone
-hypothyroidism: levothyroxine
Which labs to check for PD-1 drugs?
-LFT, AST/ALT
-TSH (is elevated), sometimes T4
-cortisol levels to measure adrenal insufficiency
check every cycle (every 4 weeks)
What is the Adjuvant treatment approach for early-stage NSCLC for a patient with Adenocarcinoma (large cell) if cure is the goal?
Cisplatin doublet (Cisplatin is more effective, also more toxic)
Cisplatin + Pemetrexed
What is the Adjuvant treatment approach for early-stage NSCLC for a patient with Squamous cells if a cure is the goal?
Cisplatin doublet (Cisplatin is more effective, also more toxic)
Cisplatin + gemcitabin
Cisplatin + docetxal
Cisplatin + vinorelbine
Which drug is used to prevent myelosuppression from pemetrexed?
Folic acid and Vitamin B12
for skin reaction: Dexamethasone
Drug of choice for EGFR mutated NSCLC?
(palliative)
Osimertinib (Tagrisso)
(EGFR TKI)
Drug of choice for NSCLC with ALK rearrangements?
(palliative)
Alectininb
(ALK TKI)
Drug of choice for NSCLC with ROS1 rearrangements?
(palliative)
Crizotinib
(ROS1 TKI)
Drug of choice for BRAF V600E mutated NSCLC?
(palliative)
Dabrafenib + trametinib
(BRAF TKI + MEK TKI)
Drug of choice for NSCLC with other actionable mutations?
(palliative)
Selpercatinib
capmatinib
sotorasib
Drug of choice for NSCLC with Non-squamous cells?
(palliative)
!!!
Non-squamous -> usually adenocarcinoma
Carboplatin + pemetrexed + immunotherapy
Drug of choice for NSCLC with Squamous cells?
(palliative)
Carboplatin + paclitaxel + immunotherapy
Drug of choice for NSCLC with high PD-L1 expression?
(palliative)
Pembrolizumab (PD-1 inhibitor)
Drug option for patients who are bad candidates for cytotoxic agents (bad kidney or liver function)
go with immune inhibitors -> but more immune-related events
nevoliumab + ipilimumab
Drug regimen for adenocarcinoma/large cell histology
Platinum/pemetrexed + IO (immunecheck inhibitor); or nivolumab + ipilimumab (CTLA-4 inhibitor)
A patient has received carboplatin + paclitaxel + pembrolizumab. 4 days after cycle 2 she was admitted to the hospital with diarrhea and dehydration. How should this be managed?
probably immune-related:
L
E
GI (diarrhea, colitis)
S
IV fluids + steroids (methylprednisolone) 1mg/kg BID
What is the most effective treatment for NSCLC?
Surgery
-most patients are not surgical candidates
What is the first-line treatment for SCLC?
Cisplatin + etoposide + XRT (radiation)
for palliative treatment:
-Carboplatin/etoposide + atezolizumab (or durvalumab, PD-L1 inhibitors); PD-1 have not worked that well
