Pembrolizumab

In a multinational double-blind trial (MK-3475-054/KEYNOTE-054 [NCT02362594]), patients with completely resected stage IIIA, IIIB, or IIIC melanoma were randomly assigned (1:1) to receive either pembrolizumab or placebo.[25][Level of evidence B1] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. If recurrence was documented, patients could cross over or repeat treatment with pembrolizumab. Pembrolizumab was given as an IV infusion of 200 mg every 3 weeks, for a total of 18 doses (approximately 1 year). A total of 1,019 patients were randomly assigned: 514 to pembrolizumab and 505 to placebo. Baseline characteristics were balanced in the two treatment groups. Approximately 40% had ulcerated primary melanoma, 66% had macroscopic lymph node involvement, 84% had positive PD-L1 expression (melanoma score >2 by 22C3 antibody assay), and 44% had BRAF pathogenic variants.

In a multinational double-blind trial (MK-3475-054/KEYNOTE-054 [NCT02362594]), patients with completely resected stage IIIA, IIIB, or IIIC melanoma were randomly assigned (1:1) to receive either pembrolizumab or placebo.[25][Level of evidence B1] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. If recurrence was documented, patients could cross over or repeat treatment with pembrolizumab. Pembrolizumab was given as an IV infusion of 200 mg every 3 weeks, for a total of 18 doses (approximately 1 year). A total of 1,019 patients were randomly assigned: 514 to pembrolizumab and 505 to placebo. Baseline characteristics were balanced in the two treatment groups. Approximately 40% had ulcerated primary melanoma, 66% had macroscopic lymph node involvement, 84% had positive PD-L1 expression (melanoma score >2 by 22C3 antibody assay), and 44% had BRAF pathogenic variants.

The EORTC Independent Data Monitoring Committee reviewed the unblinded results at an amended interim analysis when 351 events (recurrences or deaths) had occurred. The results were positive, and the interim analysis of RFS became the final analysis.

In a multinational double-blind trial (MK-3475-054/KEYNOTE-054 [NCT02362594]), patients with completely resected stage IIIA, IIIB, or IIIC melanoma were randomly assigned (1:1) to receive either pembrolizumab or placebo.[25][Level of evidence B1] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. If recurrence was documented, patients could cross over or repeat treatment with pembrolizumab. Pembrolizumab was given as an IV infusion of 200 mg every 3 weeks, for a total of 18 doses (approximately 1 year). A total of 1,019 patients were randomly assigned: 514 to pembrolizumab and 505 to placebo. Baseline characteristics were balanced in the two treatment groups. Approximately 40% had ulcerated primary melanoma, 66% had macroscopic lymph node involvement, 84% had positive PD-L1 expression (melanoma score >2 by 22C3 antibody assay), and 44% had BRAF pathogenic variants.

At the amended interim analysis with a median follow-up of 15 months, the 12-month RFS rate was 75.4% (95% CI, 71.3%–78.9%) in the pembrolizumab group versus 61.0% (95% CI, 56.5%–65.1%) in the placebo group.

In a multinational double-blind trial (MK-3475-054/KEYNOTE-054 [NCT02362594]), patients with completely resected stage IIIA, IIIB, or IIIC melanoma were randomly assigned (1:1) to receive either pembrolizumab or placebo.[25][Level of evidence B1] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. If recurrence was documented, patients could cross over or repeat treatment with pembrolizumab. Pembrolizumab was given as an IV infusion of 200 mg every 3 weeks, for a total of 18 doses (approximately 1 year). A total of 1,019 patients were randomly assigned: 514 to pembrolizumab and 505 to placebo. Baseline characteristics were balanced in the two treatment groups. Approximately 40% had ulcerated primary melanoma, 66% had macroscopic lymph node involvement, 84% had positive PD-L1 expression (melanoma score >2 by 22C3 antibody assay), and 44% had BRAF pathogenic variants.

An update of the primary end point of RFS with a median follow-up 3.5 years showed an RFS rate of 59.8% (95% CI, 55.3%–64.1%) in the pembrolizumab group versus 41.4% (95% CI, 39.2%–48.8%) in the placebo group (HR, 0.59; 95% CI, 0.49–0.73).[29]

In a multinational double-blind trial (MK-3475-054/KEYNOTE-054 [NCT02362594]), patients with completely resected stage IIIA, IIIB, or IIIC melanoma were randomly assigned (1:1) to receive either pembrolizumab or placebo.[25][Level of evidence B1] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. If recurrence was documented, patients could cross over or repeat treatment with pembrolizumab. Pembrolizumab was given as an IV infusion of 200 mg every 3 weeks, for a total of 18 doses (approximately 1 year). A total of 1,019 patients were randomly assigned: 514 to pembrolizumab and 505 to placebo. Baseline characteristics were balanced in the two treatment groups. Approximately 40% had ulcerated primary melanoma, 66% had macroscopic lymph node involvement, 84% had positive PD-L1 expression (melanoma score >2 by 22C3 antibody assay), and 44% had BRAF pathogenic variants.

Pembrolizumab maintained its effect regardless of PD-L1 expression or BRAF pathogenic variant status.

In a multinational double-blind trial (MK-3475-054/KEYNOTE-054 [NCT02362594]), patients with completely resected stage IIIA, IIIB, or IIIC melanoma were randomly assigned (1:1) to receive either pembrolizumab or placebo.[25][Level of evidence B1] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. If recurrence was documented, patients could cross over or repeat treatment with pembrolizumab. Pembrolizumab was given as an IV infusion of 200 mg every 3 weeks, for a total of 18 doses (approximately 1 year). A total of 1,019 patients were randomly assigned: 514 to pembrolizumab and 505 to placebo. Baseline characteristics were balanced in the two treatment groups. Approximately 40% had ulcerated primary melanoma, 66% had macroscopic lymph node involvement, 84% had positive PD-L1 expression (melanoma score >2 by 22C3 antibody assay), and 44% had BRAF pathogenic variants.

Approximately 14% of patients discontinued pembrolizumab due to an adverse event. Grade 3, 4, or 5 adverse events considered to be related to pembrolizumab occurred in 15% of patients. There was one death due to treatment (myositis).