Pembro, bro.

Top Line: Does pembrolizumab improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)?
The Study: If you thought to yourself, “umm, yes,” you’re right. But that conclusion was based on the abstract of the KEYNOTE-048 trial. Until now. Here we have the whole shebang. Nearly 900 patients were randomized to receive either: 1) platinum + 5FU + cetuximab, 2) platinum + 5FU + pembro, or 3) pembro alone. Chemo was given for 6 cycles, and both cetuximab and pembrolizumab were continued until disease progression. 85% of patients had a combined positive score  of ≥1 (aka CPS, aka the ratio of PD-L1 positive cells to viable tumor cells x100), and 43% had a CPS of ≥20. There were two big takeaways. First, pembro alone or with chemo clearly improved overall survival among patients with a CPS ≥1. Across everyone, pembro alone was still non-inferior and pembro + chemo remained superior when compared to cetuximab. Weirdly, patients on pembro alone had a numerically higher rate of disease progression at a median of 3 versus 5 months in the chemo arms. But wait. Pembro responses, while fewer in number, were more likely to be complete and/or durable. So...is the “overall” benefit of pembro driven only by this small subset with a tremendous response? The authors say no. They hypothesize that early exposure to immune checkpoint inhibition (ICI) has beneficial downstream effects with subsequent lines of therapy. A practical concern for med oncs is what regimen to use in symptomatic patients needing a quick response. Beam on, anyone? Anyone?
TBL: Despite producing less disease response, pembro alone or with chemo significantly improves overall survival in patients with recurrent and/or metastatic HNSCC. | Burtness, Lancet 2019

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