As reported in The Lancet Oncology by Georgina V. Long, MBBS, PhD, and colleagues, an analysis from the phase III KEYNOTE-716 trial has shown significant improvement in the secondary endpoint of distant metastasis–free survival with adjuvant pembrolizumab vs placebo in resected stage IIB or IIC cutaneous melanoma.
Georgina V. Long, MD, PhD
An interim analysis of the trial supported the December 2021 approval of pembrolizumab in the adjuvant treatment of adult and pediatric (≥ 12 years old) patients with stage IIB or IIC melanoma following complete resection on the basis of improved recurrence-free survival.
Study Details
In the double-blind trial, 976 patients aged ≥ 12 years from sites in 16 countries were randomly assigned between September 2018 and November 2020 to receive pembrolizumab (n = 487) at 200 mg (2 mg/kg up to a maximum of 200 mg in pediatric patients) or placebo (n = 489) every 3 weeks for up to 17 cycles. The current report provides results of the prespecified third interim analysis of distant metastasis–free survival.
Key Findings
At data cutoff for the analysis (in January 2022), median follow-up was 27.4 months (interquartile range = 23.1–31.7 months). Pembrolizumab significantly improved distant metastasis–free survival vs placebo (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.47–0.88, P = .0029). Median distant metastasis–free survival was not reached (95% CI = not reached to not reached) in either group.
Rates at 24 months were 88% (95% CI = 84%–91%) vs 82% (95% CI = 78%–86%). At 36.7 months, restricted mean survival time was 33.3 months for the pembrolizumab group and 31.5 months for the placebo group (restricted mean survival time difference = 1.8 months, 95% CI = 0.6–3.1 months, P = .0039).
The most common treatment-related grade ≥ 3 adverse events were hypertension (3% of pembrolizumab group vs 4% of placebo group), diarrhea (2% vs < 1%), rash (1% vs < 1%), autoimmune hepatitis (1% vs < 1%), and increased lipase (1% vs 2%). Treatment-related serious adverse events occurred in 10% vs 2% of patients. No treatment-related deaths were reported.
The investigators concluded: “Adjuvant pembrolizumab is an efficacious treatment option for resected stage IIB and IIC melanoma, with significant improvement in distant-metastasis free survival versus placebo … with an adverse event profile consistent with previous studies of pembrolizumab. The overall benefit–risk of pembrolizumab continues to be positive in the adjuvant setting.”
Georgina V. Long, MD, of the Melanoma Institute Australia, The University of Sydney, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit thelancet.com.
