Georgina V. Long, MD, PhD, on Melanoma: Distant Metastasis–Free Survival With Adjuvant Pembrolizumab

Keynote 716 is a phase three randomized trial of adjuvant pembrolizumab versus placebo in resected stage 2B and 2C melanoma. Historically from retrospective studies, stage 2B and C melanoma has been thought to be not as high risk as it actually is. In fact, many patients recur at 24 months and beyond, and these patients have very poor outcomes. So I'm reporting the distant metastasis free survival from this trial. We've previously reported on the relapse free survival on two previous analyses. And what we see is pembrolizumab significantly improves the distant metastasis free survival compared with placebo with a hazard ratio of 0.64, this represents a 36% reduction in the risk of recurrence, and a P value of 0.0029. This is highly significant. We also see on the 24 month and the 12 month landmark distant metastasis free survival rates, a significant increase compared with placebo of pembrolizumab. What's more in this study when we look at the subgroups, key subgroups, every subgroup favors pembrolizumab compared with placebo for the distant metastasis free survival, including the T subcategories 3B, 4A and 4B, as well as the US geographical region. We also see a sustained improvement in the relapse free survival. So at this analysis, this is the third analysis for the relapse free survival. It was the first for distant metastasis free survival. We see a hazard ratio of 0.64 and continued separation of the Kaplan-Meier curves for the relapse-free survival, meaning that adjuvant pembrolizumab significantly decreases the risk of recurrence for patients with resected stage 2B and 2C melanoma. So what are the next steps? The next steps are that we will continue to follow up with this trial and look at the overall survival benefit. In the design of this trial, we had crossover at recurrence. So patients were initially randomized to placebo versus pembrolizumab. But if they recurred, they were unblinded. If they were on the placebo arm or on the pembrolizumab arm, and they had their last dose of pembrolizumab six months or further prior, they were eligible to cross over to pembrolizumab. So we'll also be watching for the overall survival in the coming years. The take home message is that adjuvant pembrolizumab significantly improves both the relapse free survival and the distant metastasis free survival, and should be considered for patients with resected stage 2B and 2C melanoma.