Pembrolizumab for Advanced Melanoma: Efficacy and Toxicity

This PD-1 inhibitor is effective for treating melanoma, though it can be highly toxic and there is a lack of biomarkers for predicting a response.
This PD-1 inhibitor is effective for treating melanoma, though it can be highly toxic and there is a lack of biomarkers for predicting a response.

Historically, long-term survival of patients with advanced melanoma was less than 10%.1 Treatment of this disease has, however, advanced quickly over recent years, particularly with the introduction and development of immunotherapeutic agents and inhibitors of BRAF and MEK.

Pembrolizumab, a PD-1 inhibitor, has proven effective in this treatment setting, though there is some controversy whether it should be favored over other immunotherapeutic options like nivolumab and ipilimumab.2

For the phase 2 Keynote-002 study (ClinicalTrials.gov identifier: NCT01704287), a randomized trial of pembrolizumab vs chemotherapy in ipilimumab-refractory melanoma, patients were randomly assigned to receive pembrolizumab 2 mg/kg once every 3 weeks, pembrolizumab 10 mg/kg once every 3 weeks, or investigator's choice of chemotherapy.

Progression-free survival (PFS) was improved in both the 2 mg/kg (hazard ratio [HR], 0.57; 95% CI, 0.45-0.73; P < .0001) and the 10 mg/kg (HR, 0.50; 95% CI 0.39-0.64; P < .0001) pembrolizumab arms.3

PFS at 6 months was 34% in the 2 mg/kg and 38% in the 10 mg/kg pembrolizumab arms vs 16% in the chemotherapy arm. Grade 3 or 4 treatment-related adverse events occurred in 11% of patients in the 2 mg/kg pembrolizumab arm, in 14% of patients in the 10 mg/kg pembrolizumab arm, and in 26% of those in the chemotherapy arm.3

In the controlled phase 3 Keynote-006 (ClinicalTrials.gov identifier: NCT01866319), patients with advanced melanoma were randomly assigned to receive pembrolizumab 10 mg/kg every 2 weeks, pembrolizumab 10 mg/kg every 3 weeks, or ipilimumab 3 mg/kg every 3 weeks. Enrolled patients had a maximum of 1 previous systemic therapy.4

Estimated 6-month PFS was 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (HR for progressed disease, 0.58; P < .001 for both pembrolizumab arms vs ipilimumab).

Estimated 12-month survival was 74.1% for pembrolizumab every 2 weeks, 68.4% for pembrolizumab every 3 weeks, and 58.2% for ipilimumab (HR for death for pembrolizumab every 2 week, 0.63; HR for pembrolizumab every 3 weeks, 0.69).

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