Previously, adjuvant pembrolizumab demonstrated improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB or IIC melanoma, compared to placebo. This final analysis reaffirms the manageable safety profile and substantial clinical benefits of pembrolizumab over placebo, supporting the use of pembrolizumab adjuvant therapy in patients with resected stage IIB or IIC melanoma.
In the PHASE III KEYNOTE-716 trial, pembrolizumab was investigated as adjuvant therapy for patients with resected stage IIB or IIC melanoma. Initial interim analysis revealed a significant improvement in recurrence-free survival (RFS) compared to placebo, while subsequent analysis showed a notable enhancement in distant metastasis-free survival (DMFS). These compelling findings led to the approval of pembrolizumab as adjuvant therapy for stage IIB or IIC melanoma by the FDA and EMA. This report presents the results of the protocol-specified fourth interim analysis of KEYNOTE-716, offering final DMFS data and updated RFS outcomes.
The phase III KEYNOTE-716 study included patients aged ≥12 years with newly diagnosed, resected, histologically confirmed, stage IIB (T3b or T4a) or IIC (T4b) cutaneous melanoma without regional lymph node involvement. Patients were randomly assigned (1:1) to receive pembrolizumab 200 mg (2 mg/kg up to 200 mg in pediatric patients) or placebo intravenously once every three weeks for 17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS, while secondary endpoints included DMFS, safety and tolerability.
In total, 976 patients were randomly assigned to receive pembrolizumab (n = 487) or placebo (n = 489). Pembrolizumab continued to demonstrate a clinically meaningful DMFS and RFS benefit compared with placebo after a median follow-up of 39.4 months. At the 36-month mark, DMFS was reported at 84.4% vs. 74.7% in the pembrolizumab and placebo groups, respectively (HR[95%CI]: 0.59 [0.44-0.79]), while RFS stood at 76.2% vs. 63.4% (HR[95%CI]: 0.62 [0.49-0.79]). DMFS and RFS results were consistent across most prespecified subgroups, including stage IIB and stage IIC melanoma. The safety profile of pembrolizumab was manageable and consistent with previous reports. Treatment-related adverse events (TRAEs) were reported in 82.6% vs. 63.6% of patients in the pembrolizumab and placebo arms, respectively. TRAEs resulted in treatment discontinuation in 15.9% vs. 2.5% of the cases, with no TRAEs leading to death. Immune-mediated AEs and infusion reactions occurred in 37.9% vs. 9.5% of patients.
In the final DMFS analysis of KEYNOTE-716, pembrolizumab continued to demonstrate manageable safety and a clinically meaningful DMFS and RFS benefit compared with placebo, supporting the use of pembrolizumab adjuvant therapy in patients with resected stage IIB or IIC melanoma.
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