Top Line: How does pembrolizumab fare in the treatment of resected stage III melanoma?
The Study: A few months back we learned that nivolumab improved recurrence-free survival (RFS) and reduced toxicity in patients with resected stage III melanoma. Among BRAF-mutated patients, dabrafenib and trametinib did the same. When these results were reported, the arms from the ongoing KEYNOTE-054 trial were unblinded, and an interim RFS analysis was performed. In this study, patients with resected nodal disease were randomized to placebo or pembro for roughly 12 months or until progression. At the interim analysis, pembro improved RFS at 12 months from 61→75%. The benefit persisted for tumors with or without PD-L1 expression and with or without BRAF mutations. These results are pretty comparable to those with nivo, including a similar rate (~15%) of toxicity. Yet to be hashed out are the patterns of failure. Rates of distant disease are definitely slashed by immunotherapy, but it’s less clear how locoregional recurrences are effected. So is less (or more?) aggressive local therapy warranted in the setting of more durable systemic control?
Bottom Line: Pembro, like nivo, improves RFS at 12 months by 10-15% for resected stage III melanoma with similar rates of toxicity. | Eggermont, N Engl J Med 2018


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