Pembrolizumab for Melanoma: What Patients Need to Know

Advanced melanoma was once associated with very limited treatment options and poor long-term outcomes. The arrival of checkpoint inhibitors - and pembrolizumab in particular - has changed that profoundly. Five-year survival rates that would have been unimaginable a decade ago are now documented in clinical trials. Here is what melanoma patients need to understand about the evidence.

The KEYNOTE-001 five-year data

KEYNOTE-001 was the first major trial evaluating pembrolizumab in melanoma, enrolling patients with advanced disease who had either previously received treatment or were treatment-naive. The five-year overall survival data - published in 2019 - showed that approximately 34% of all enrolled patients were alive at five years. Among patients who had not previously received treatment, the rate was around 41%.

To appreciate what this represents: historically, five-year survival in advanced melanoma was approximately 5% with treatments available before immunotherapy. The improvement documented in KEYNOTE-001 is one of the most dramatic outcomes seen in any solid tumour over the same time period.

KEYNOTE-006: Pembrolizumab vs ipilimumab

KEYNOTE-006 compared pembrolizumab directly against ipilimumab, an earlier checkpoint inhibitor (targeting CTLA-4 rather than PD-1). Pembrolizumab produced a significantly higher objective response rate, longer progression-free survival, and better overall survival. Importantly, it also had a lower rate of high-grade (grade 3-4) immune-related side effects. The results established pembrolizumab as the preferred monotherapy option for advanced melanoma.

Adjuvant use after surgery

Pembrolizumab is also approved in the adjuvant setting - used after surgical removal of high-risk melanoma to reduce the chance of recurrence. The KEYNOTE-054 trial demonstrated a significant improvement in recurrence-free survival compared to placebo in patients with Stage III resected melanoma. Adjuvant pembrolizumab is now a standard option in this setting for patients at high risk of recurrence after surgery.

BRAF mutations and treatment choices

Approximately 40-50% of cutaneous melanomas carry a BRAF V600 mutation. Patients with BRAF-mutated disease have an additional treatment option - targeted therapy with BRAF and MEK inhibitors - which can produce rapid responses. The sequencing of targeted therapy and immunotherapy in BRAF-mutated melanoma is an active area of clinical decision-making, and the right approach depends on factors including disease urgency, patient preference, and individual clinical characteristics.

For BRAF wild-type patients, pembrolizumab is typically the first treatment offered for advanced disease. For BRAF-mutated patients, an oncologist will advise on whether to start with immunotherapy, targeted therapy, or consider them in combination.