A 52-year-old man presents with a 2.5 cm pigmented lesion on his back with irregular borders and mixed colors. Biopsy confirms cutaneous melanoma with a Breslow thickness of 3.2 mm and no ulceration. He is found to be BRAF V600E mutation-positive on molecular testing. After complete staging shows no distant metastases (Stage IIIB), he undergoes wide local excision and sentinel lymph node biopsy. What is the drug of choice for adjuvant therapy in this patient?

Explanation

## Adjuvant Therapy for Stage III Melanoma **Key Point:** Nivolumab (anti-PD-1 checkpoint inhibitor) is the current standard of care for adjuvant treatment of resected Stage III melanoma, regardless of BRAF mutation status. ### Evidence & Guideline Basis The CheckMate 238 trial (2017) demonstrated that nivolumab significantly improved recurrence-free survival (RFS) and overall survival (OS) compared to interferon-alpha in patients with resected Stage IIIB–C melanoma. This led to FDA approval and adoption by ASCO, NCCN, and ESMO as the preferred adjuvant agent. **High-Yield:** Nivolumab is now preferred over: - Interferon-alpha (older standard; lower efficacy, more toxicity) - Dacarbazine (reserved for metastatic disease; not used adjuvantly) - Temozolomide (not standard adjuvant therapy) ### Treatment Algorithm for Resected Stage III Melanoma ```mermaid flowchart TD A[Resected Stage III Melanoma]:::outcome --> B{BRAF mutation status?}:::decision B -->|BRAF V600E/K mutant| C[Checkpoint inhibitor first-line]:::action B -->|BRAF wild-type| D[Checkpoint inhibitor]:::action C --> E[Nivolumab or Pembrolizumab]:::action D --> E E --> F[Adjuvant monotherapy for 1 year]:::action F --> G[Improved RFS & OS]:::outcome ``` ### Comparison of Adjuvant Options | Agent | Mechanism | Stage | Evidence | Toxicity | |-------|-----------|-------|----------|----------| | **Nivolumab** | Anti-PD-1 | III (resected) | CheckMate 238 (superior RFS) | Immune-mediated (manageable) | | **Pembrolizumab** | Anti-PD-1 | III (resected) | KEYNOTE-054 (similar efficacy) | Immune-mediated | | **Interferon-α** | Cytokine | III (resected) | Older standard (lower RFS) | Flu-like, depression, myelosuppression | | **Dacarbazine** | Alkylating agent | IV (metastatic) | Not adjuvant standard | Myelosuppression, nausea | | **Temozolomide** | Alkylating agent | IV (metastatic) | Not adjuvant standard | Myelosuppression | **Clinical Pearl:** BRAF mutation status does NOT change the choice of adjuvant immunotherapy. BRAF inhibitors (vemurafenib, dabrafenib) + MEK inhibitors are reserved for metastatic BRAF-mutant disease, not adjuvant therapy. **Tip:** In NEET PG exams, when you see "resected Stage III melanoma" + "adjuvant therapy," the answer is a checkpoint inhibitor (nivolumab or pembrolizumab). Interferon-alpha is outdated for this indication.