Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Pooled analyses after long-term follow-up in KEYNOTE-012.

6012 Background: The PD-1 pathway is a key mechanism by which R/M HNSCC tumors evade immune surveillance. Pembrolizumab (pembro), an anti–PD-1 antibody, showed promising antitumor activity in R/M HNSCC in KEYNOTE-012 (NCT01848834). We present a pooled analysis of efficacy and safety of pembro after long-term follow-up in R/M HNSCC pts in this study. Methods: Pts had R/M HNSCC, measurable disease by RECIST v1.1, and ECOG PS 0-1. The initial (I) cohort enrolled PD-L1+ pts; expansion (E) cohort enrolled pts regardless of PD-L1 status. Pembro 10 mg/kg Q2W (I) or 200 mg Q3W (E) was given for 24 mo or until disease progression, unacceptable safety, or investigator/pt decision. Response was assessed every 8 wk. AEs were graded using CTCAE v4.0. Primary end point was ORR (RECIST v1.1) per central imaging vendor review. Secondary end points included PFS, OS, and duration of response (DOR). Pts who received ≥ 1 dose of pembro were included in these pooled analyses. Results: 192 R/M HNSCC pts were enrolled and received pembro (I = 60; E = 132); the last pt was enrolled on Oct 8, 2014. 32 (17%) pts (I = 6; E = 26) were still on treatment as of Sept 1, 2015. Median age was 60 y; 83% were male; 70% had ECOG PS 1; 61% received ≥ 2 therapies for recurrent disease. ORR (confirmed) was 17.7% (95% CI, 12.6%-23.9%; 7 CRs, 27 PRs). Median follow-up duration in responders was 12.5 mo (range, 8.4-24.4). At data cutoff, median DOR was not yet reached (range, 1.8+ to 21.8+ mo); responses were ongoing in 22 (76%) pts. Responses of ≥ 6 mo and ≥ 12 mo were noted in 25 pts and 4 pts. 33 (17%) pts achieved stable disease. ORR was 21.9% (95% CI, 12.5%-34.0%) in HPV+ pts and 15.9% (95% CI, 10.0%-23.4%) in HPV- pts. Median OS was 8.5 mo (95% CI, 6.5-10.5). The 6-mo PFS rate was 24.9%. Treatment-related AEs (TRAEs) occurred in 122 (64%) pts; 23 (12%) pts had a grade 3-4 TRAE. No pts died because of a TRAE. ALT and AST increases were the only grade 3-4 TRAEs in > 2 pts. Conclusions: Robust antitumor activity, with durable responses up to ~2 y and promising survival during long-term follow-up, suggests pembro given as 200 mg Q3W or 10 mg/kg Q2W is an active treatment for R/M HNSCC regardless of PD-L1 status. Pembro was well tolerated in R/M HNSCC pts. Clinical trial information: NCT01848834.