1. Epidemiology & Risk Factors
- NSCLC (~85%) vs SCLC (~15%)
- Major risk factor: smoking (tobacco)
- Environmental/occupational exposures: radon, asbestos, air pollution
- Genetic mutations: EGFR, ALK, ROS1, KRAS
2. Histology & Molecular Testing
- NSCLC subtypes: adenocarcinoma, squamous cell, large cell
- SCLC: central, aggressive, strongly smoking-related
- Molecular markers for NSCLC adenocarcinoma:
- EGFR mutations → TKIs (erlotinib, gefitinib, afatinib)
- ALK rearrangements → ALK inhibitors (crizotinib, alectinib, lorlatinib)
- ROS1, BRAF, KRAS mutations
- PD-L1 expression → guides immunotherapy (pembrolizumab, atezolizumab)
3. Staging
- NSCLC: TNM staging I–IV
- Stage I-II: surgery ± adjuvant chemo
- Stage III: chemoradiation ± consolidation
- Stage IV: systemic therapy (targeted, immunotherapy, chemo)
- SCLC: limited vs extensive stage
- Limited: confined to one hemithorax → chemo + thoracic radiation
- Extensive: metastatic → chemo ± immunotherapy
4. First-Line Therapy
- NSCLC (nonsquamous):
- Driver mutation positive: targeted therapy (EGFR/ALK)
- No driver mutation: platinum doublet chemo ± immunotherapy (pemetrexed preferred in nonsquamous)
- NSCLC (squamous): platinum doublet (carboplatin + paclitaxel or gemcitabine) ± immunotherapy
- SCLC:
- Limited: cisplatin/carboplatin + etoposide + concurrent thoracic radiation
- Extensive: cisplatin/carboplatin + etoposide ± immunotherapy
5. Maintenance & Second-Line Therapy
- NSCLC:
- Maintenance: pemetrexed ± immunotherapy for nonsquamous; pembrolizumab, gemcitabine, or docetaxel for squamous
- Second-line: docetaxel, immunotherapy if not previously given
- SCLC: topotecan for relapsed disease
6. Drug Class & Key Differences
- Chemotherapy: myelosuppression, renal/hepatic toxicity, nausea, neuropathy
- Targeted therapy: mutation-specific, LFTs, rash, diarrhea, cardiotoxicity (ALK TKIs)
- Immunotherapy: immune-related adverse events → thyroiditis, colitis, hepatitis, pneumonitis
7. Pharmacist-Specific Considerations
- Dosing adjustments: renal/hepatic function for chemo and TKIs
- Drug interactions: CYP3A4 (EGFR and ALK TKIs), anticoagulants with chemo
- Monitoring: CBC, LFTs, ECG, electrolytes, thyroid function, symptoms of immune toxicity
- Supportive care: antiemetics, hydration (cisplatin), growth factor support if indicated
- Patient education: oral TKIs, adherence, toxicity recognition