1136PPhase III KEYNOTE-048 study of first-line (1L) pembrolizumab (P) for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Asia vs non-Asia subgroup (subgrp) analysis

Abstract Background KEYNOTE-048 (NCT02358031) is a randomized, open-label, phase 3 trial of P or P + chemotherapy (C) vs EXTREME (E) as 1L therapy for R/M HNSCC. At 2nd interim analysis, overall survival (OS) was significantly longer with P than E in patients (pts) with PD-L1 combined positive score (CPS) ≥20 (P = 0.0007) and CPS ≥1 (P = 0.0086) and was noninferior in the total population (pop). P+C significantly improved OS vs E in the total pop (P = 0.0034). Safety was favorable or similar to that of E. Methods Pts with R/M HNSCC not curable by local therapy and with no prior systemic therapy were randomized (1:1:1) to P 200 mg Q3W, P+C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/day for 4 days Q3W), or E (cetuximab 400 mg/m2 loading dose with 250 mg/m2 subsequent infusion QW + C) until progressive disease, unacceptable toxicity, 6 cycles of C, or 24 months of P. Primary end points were progression-free survival and OS. Data cutoff date was June 13, 2018. Results Efficacy is reported in the table. Gr 3-5 drug-related AE rates with P vs E were 28.6% vs 76.9% in the Asia subgrp and 13.9% vs 67.2% in the non-Asia subgrp; rates with P+C vs E were 71.9% vs 76.9% in the Asia subgrp and 70.8% vs 67.2% in the non-Asia subgrp. Conclusions P vs E showed favorable OS in Asia and non-Asia subgrps, regardless of PD-L1 status; responses were durable, particularly among all non-Asia subgrps; safety was favorable. P+C vs E showed favorable OS in pts with CPS ≥20 in Asia and non-Asia subgrps regardless of PD-L1 status, durable responses, and similar safety. Clinical trial identification NCT02358031. Editorial acknowledgement Doyel Mitra, PhD, and Dana Francis, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Table: 1136PAsia, CPS ≥20Asia, CPS ≥1Asia, Total PopulationNon-Asia, CPS ≥20Non-Asia, CPS ≥1Non-Asia, Total PopulationP vs E n = 22 vs 23P+C vs E n = 22 vs 21P vs E n = 48 vs 46P+C vs E n = 45 vs 43P vs E n = 56 vs 53P+C vs E n = 57 vs 49P vs E n = 111 vs 99P+C vs E n = 104 vs 89P vs E n = 209 vs 209P+C vs E n = 197 vs 192P vs E n = 245 vs 247P+C vs E n = 224 vs 229OS: HR (95% CI )0.39 (0.19-0.80)0.80 (0.41-1.58)0.80 (0.51-1.27)1.13 (0.71-1.79)0.74 (0.48-1.13)1.03 (0.68-1.58)0.75 (0.54-1.04)0.68 (0.48-0.96)0.76 (0.61-0.95)0.6