Melanoma Overview for Oncology Pharmacist
| Aspect | Key Points |
|---|---|
| Definition | Aggressive malignant tumor of melanocytes; most lethal type of skin cancer. |
| Epidemiology | Less common than basal or squamous cell carcinoma, but accounts for majority of skin cancer deaths. Risk factors: UV exposure, fair skin, family history, multiple nevi, immunosuppression. |
| Staging | Based on AJCC TNM system: tumor thickness (Breslow depth), ulceration, lymph node involvement, metastasis. Stages I–IV. |
| Molecular Markers | ~50% have BRAF V600E/K mutation; others include NRAS, KIT, and c-KIT. Marker testing is essential to guide therapy. |
| Treatment by Stage | – Early-stage (I–II): surgical excision ± sentinel lymph node biopsy. – Stage III (regional nodes): surgery + adjuvant immunotherapy or targeted therapy (if BRAF+). – Stage IV (metastatic): systemic therapy (immunotherapy or targeted therapy). |
| Immunotherapy | – Checkpoint inhibitors: → PD-1 inhibitors: nivolumab, pembrolizumab (preferred 1st-line) → CTLA-4 inhibitor: ipilimumab (used in combo with nivolumab in high-risk or advanced disease) – Toxicities: immune-related adverse events (colitis, pneumonitis, hepatitis, endocrinopathies) require early recognition and steroid management. |
| Targeted Therapy (for BRAF V600+) | – BRAF inhibitors: vemurafenib, dabrafenib, encorafenib – MEK inhibitors: trametinib, cobimetinib, binimetinib – Typically given as BRAF + MEK combination to improve survival and reduce resistance. |
| Other Options | – Oncolytic virus (Talimogene laherparepvec, T-VEC) for unresectable cutaneous/subcutaneous lesions. – Chemotherapy (dacarbazine, temozolomide) rarely used; limited efficacy, mostly historical. |
| Role of Pharmacist | – Ensure biomarker testing (BRAF mutation) is performed before initiating systemic therapy. – Manage immune-related toxicities (early detection, steroid initiation, tapering). – Counsel on adverse effects: fever, rash (BRAF/MEK); fatigue, diarrhea (immunotherapy). – Support adherence, especially in oral targeted therapies. |
| Monitoring | – LFTs, thyroid function, glucose, cortisol (immune therapy) – Dermatologic and ocular exams (BRAF/MEK) – ECG for QT prolongation risk (vemurafenib, cobimetinib). |
Key Takeaway for Oncology Pharmacist:
- Always check BRAF mutation status before systemic therapy.
- Immunotherapy (PD-1 ± CTLA-4 inhibitors) is frontline in most advanced cases.
- Targeted therapy (BRAF + MEK inhibitors) is highly effective for BRAF-mutated melanoma.
- Close monitoring for immune-related adverse events is critical to patient safety.