Lung Cancer

Question 1

types of lung cancer

Answer 1

Small Cell (SCLC)
Non-Small Cell (NSCLC)
- Squamous
- Non- Squamous (Large cell carcinoma & Adenocarcinoma)

Question 2

Signs and symptoms

Answer 2

Pulmonary
- cough
- dyspnea
- chest pain
Extra-pulmonary
- fatigue
- weight loss
- anorexia
Disseminated disease
- Neurologic (CNS metastases)
Paraneoplastic syndromes
- Hypercalcemia and SIADH

Question 3

SCLC staging

Answer 3

Limited
- confined to 1 lung
- lymph node involvement: same side of chest
Extensive stage
- involves both lungs
- lymph node involvement: both sides of chest
- extra pulmonary metastases

Question 4

Treatment for Local NSCLC Stage 1

Answer 4

Surgery

Question 5

Treatment for Local NSCLC Stage 2

Answer 5

Surgery followed by adjuvant therapy
- platinum based reg for 4 cycles
- Osimertinib (EGFR +)
- Atezolizumab (PDL1 >/= 1%)
Neoadjuvant therapy for operable yet difficult to resect tumors
- platinum based reg +/- nivolumab for 4 cycles
Radiation therapy
- reserved for inoperable tumors
- concurrent chemo preferred

Question 6

Treatment for Local NSCLC Stage 3A

Answer 6

Neoadjuvant chemo +/- nivolumab x4c cycles -> surgery or RT

Adjuvant osimertinib (EGFR+) or atezolizumab (PDL1 > 1)

Concurrent chemoradiotherapy for non-surgical candidates

Question 7

mTreatment for Local NSCLC Stage 3B-3C

Answer 7

Unresectable disease
concurrent chemoradiation is mainstay
durvalumab maintenance for 1 year upon response to chemoradiotherapy

Question 8

Cisplatin and Carboplatin ADE

Answer 8

myelosuppression
N/V
diarrhea/constipation
oral mucositis
alopecia
nephrotoxicity
ototoxicity
peripheral neuropathy

Question 9

Which ADEs occur less with Carboplatin than Cisplatin

Answer 9

N/V
Nephrotoxicity
Ototoxicity
Peripheral neuropathy

Question 10

Calvert Equation

Answer 10

Total cisplatin dose = AUC x [CrCL + 25]

for calculating CrCL
- ABW < 120% of IBW -> use IBW
- ABW > 120% of IBW -> use ABW

Question 11

Treatment for Local NSCLC Stage 4 or Relapsed Disease

Answer 11

Targetable genetic mutation (EGFR, ALK, ROS1, BRAF, NTRK, RET, MET)
- kinase inhibitor targeted to mutation

PD-L1 >/= 1%
- PD1/ PDL1 inhibitor +/- chemo

PD-L1 < 1%
- PD1/PDL1 inhibitor AND chemo

Question 12

EGFR inhibitors

Answer 12

Agents
- first gen: Erlotinib, Gefitinib, Afatinib
- second gen: dacomitinib
- third gen: osimertinib (first line)

Question 13

Osimertinib

Answer 13

3rd gen EGFR inhibitor
Dose: 80 mg QD
CYP3A4 substrate
no pH dependent absorption
ADE:
- skin rash
- dry skin
- diarrhea
- fatigue
- nail toxicity
- stomatitis
- alopecia
- conjunctivitis
- QTc prolongation
- myelosuppression

Question 14

ALK inhibitors

Answer 14

First gen: crizotinib, ceritinib
second gen: Alectinib, Brigatinib
Third gen: Lorlatinib

2nd and 3rd gen preferred

Lorlatinib shows improved potency and penetration of BBB
- neurological ADE

Question 15

Brigatinib

Answer 15

Dose: 90mg QD x 7d, 180 mg QD
QYP3A4 substrate
ADE:
- diarrhea
- fatigue
- pneumonitis
- myalgia
- HTN

Question 16

Alectinib

Answer 16

Dose: 600 mg BID
CYP3A4 substrate
ADE:
- constipation
- fatigue
- LFT abnormalities
- mood disorders
- myalgia
- HTN

Question 17

Loratinib

Answer 17

ALK inhibitor
Dose: 100mg
CYP3A4 & P-gp substrate
ADE:
- fatigue
- peripheral edema
- mood disorders
- neuropathy
- cognitive effects
- arthralgia
- dyslipidemia, weight gain

Question 18

KRAS inhibitors

Answer 18

Indicated for advanced or metastatic NSLCLC and KRAS G12C mutation
AFTER TRIAL OF 1 PRIOR THERAPY
Agents:
- Sotorasib
- Adagrasib

Question 19

Sotorasib

Answer 19

KRAS inhibitor
CYP3A4 substrate
strong P-gp inhibitor
Avoid PPIs and H2RAs (4h before and 10h after)
ADE:
- diarrhea
- nausea
- fatigue
- LFT abnormalities
- musculoskeletal pain
- dec Hgb/lymphocytes

Question 20

Adagrasib

Answer 20

KRAS inhibitor
CYP3A4 substrate
moderate inhibitor of P-gp
no pH dependent absorption
ADE:
- diarrhea
- nausea
- fatigue
- LFT abnormalities
- musculoskeletal pain
- dec Hgb / lymphocytes

• renal impairment
• edema
• QT prolongation
• interstitial lung disease / pneumonitis

Question 21

PDL1 > 50% NSCLC first line treatments

Answer 21

pembrolizumab
atezolizumab
cemiplimab

Question 22

Squamous PDL1 <50% NSCLC first line

Answer 22

Cis or Carb + Paclitaxel + Pembrolizumab

Cis or Carb + Paclitaxel + Nivolumab + Ipilimumab

Question 23

Non-squamous PDL1 < 50 NSCLC first line

Answer 23

Cis or Carb + Pemetrexed + Pembrolizumab

Cis or Carb + Pemetrexed + Nivolumab + Ipilimumab

Question 24

NSCLC 2nd line

Answer 24

No previous checkpoint inhibitor ->
- pembrolizumab
- nivolumab
- atezolizumab

Previous checkpoint inhibitor ->
- Docetaxel + Ramucirumab
- Ramucirumab + Pembrolizumab
- Docetaxel
- Pemetrexed (nonsquamous)

Question 25

Immunotherapy ADE

Answer 25

Management:
- grade 1: continue immunotherapy
- grade 2: hold immunotherapy and consider corticosteroid
- grade > 3: hold immunotherapy and give corticosteroid

Prednisone 0.5-2 mg/d until grade 1 -> taper over 1 month

ADE:
- encephalitis
- thyroiditis, hypothyroid, hyperthyroid
- mucositis
- pneumonitis
- rash
- thrombocytopenia, anemia
- myocarditis
- hepatitis
- pancreatitis
- adrenal insufficiency
- colitis
- neuropathy

Question 26

VEGF inhibitors

Answer 26

Agents: Bevacizumab, Ramucirumab
ADE:
- HTN
- thromboembolic events
- epistaxis
- major bleeds
- GI perforation
- proteinuria
- diarrhea (ramucirumab)

avoid in pts with squamous histology (bevacizumab), recent hemoptysis, on therapeutic anticoagulation, recent surgical procedure

Question 27

Chemo: Taxanes

Answer 27

Agents: paclitaxel, docetaxel
ADE:
- myelosuppression
- alopecia
- peripheral neuropathy
- mucositis
- diarrhea
- N/V
- hypersensitivity rxn (pre-med with dexamethasone, famotidine, diphenhydramine)
- peripheral edema (docetaxel) (pre-med with dexamethasone 8 mg BID day before, day of, and day after)

Question 28

Chemotherapy: Pemetrexed

Answer 28

Avoid in CrCl < 45
temporary NSAID hold
ADE:
- myelosuppression
- erythematous/pruritic rash
- fatigue
- diarrhea
- N/V
Folic acid and B12 prophylaxis
Dexamethasone 4mg BID day before, of, and after

Question 29

SCLC

Answer 29

Chemo +/- radiation
1st line:
- Cis + Etoposide
- Carb + Etoposide
- Carb + Etoposide + Atezolizumab (ext stage only)
- Carb + Eto + Durvalumab (ext stage only)
- Cis + Eto + Durvalumab

2nd line:
- Topotecan
- Lurbinectedin
- Clinical trial

Question 30

Etoposide

Answer 30

Topoisomerase II inhibitor
ADE:
- myelosuppression
- N/V
- stomatitis
- alopecia

Question 31

Topotecan

Answer 31

Topoisomerase I inhibitor
reduce dose in renal insufficiency
ADE:
- myelosuppression
- diarrhea
- N/V
- fatigue
- alopecia

Question 32

Lurbinectedin

Answer 32

SCLC chemo agent
ADE
- fatigue
- hepatic enzyme elevation
- extravasation
- nausea
- myelosuppression
- inc SCr
- musculoskeletal pain

Pretreat with dexamethasone (for hepatic enzymes) and 5-HT3 antagonist for N/V