PD-L1 CPS ≥10 population subgroup analysis of KEYNOTE-412: Pembrolizumab plus chemoradiotherapy versus placebo plus chemoradiotherapy for unresected locally advanced head and neck squamous cell carcinoma.

6063 Background: At the end-of-trial analysis of the randomized, double-blind, phase 3 KEYNOTE-412 trial (NCT03040999) in participants with unresected locally advanced (LA) head and neck squamous cell carcinoma (HNSCC), pembrolizumab plus chemoradiotherapy (CRT) was associated with a clinically meaningful event-free survival (EFS) benefit over placebo plus CRT (HR 0.79; 95% CI, 0.65-0.96) in the total population, and in participants whose tumors expressed PD-L1 CPS ≥1 (HR 0.80; 95% CI 0.64-0.98) and CPS ≥20 (HR 0.70; 95% CI, 0.49-1.00). We conducted a post hoc analysis of outcomes in the PD-L1 CPS ≥10 population. Methods: Adults with high-risk unresected LA HNSCC (T3-4 N0-3 or T1-4 N2a-3 laryngeal/hypopharyngeal/oral cavity/p16-negative oropharyngeal SCC, or T4 or N3 p16-positive oropharyngeal SCC) were randomly assigned to receive definitive CRT plus 17 cycles of pembrolizumab 200 mg or placebo intravenously every 3 weeks concurrently and after CRT. This exploratory analysis evaluated EFS and overall survival (OS) in the PD-L1 CPS ≥10 population. Results: Of 804 total participants, 382 had tumors expressing PD-L1 CPS ≥10 (n = 194, pembrolizumab group; n = 188, placebo group). As of data cutoff date (August 21, 2024), median study follow-up in the PD-L1 CPS ≥10 population was 74.1 months (range, 63.8-88.1). Median EFS was not reached (NR) in the pembrolizumab group and 61.4 months in the placebo group (HR 0.71; 95% CI, 0.53-0.97). The 60-month EFS rates were 62.4% and 50.3%, respectively. Median OS was not reached in either the pembrolizumab or the placebo group; the 60-month OS rates were 70.7% and 60.9%, respectively (HR 0.75 95% CI, 0.53-1.04). Conclusions: Results from this post hoc analysis of the KEYNOTE-412 trial with over 2 years of additional follow-up were consistent with those of the end-of-trial analysis in the overall population. For participants whose tumors expressed PD-L1 with a CPS ≥10, we observed a clinically meaningful EFS and OS benefit for pembrolizumab plus CRT over placebo plus CRT, with a numerically lower HR than reported for the overall population. Clinical trial information: NCT03040999 .