Pembrolizumab with or without chemotherapy for first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): 5-year results from KEYNOTE-048

Long-term follow-up (4 years) of the phase 3 KEYNOTE-048 (NCT02358031) study continued to demonstrate survival benefit with pembrolizumab monotherapy and pembrolizumab + chemotherapy vs EXTREME in first-line R/M HNSCC. Pembrolizumab showed significantly longer OS vs EXTREME in PD-L1 CPS ≥1. Given that pembrolizumab + chemotherapy or pembrolizumab for CPS ≥1 is standard of care for first-line R/M HNSCC in the United States, outcomes with extended follow-up are of interest. We present 5 years of follow-up in all patients (pts) from KEYNOTE-048. Pts with incurable R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab 200 mg Q3W, pembrolizumab + chemotherapy, or EXTREME. OS, PFS, ORR, and DOR were assessed in the ITT population and analyzed in PD-L1 CPS ≥1, PD-L1 CPS ≥20, and total populations. As of the February 21, 2022, data cutoff date, median follow-up was 69.2 mo (range, 61.2-81.6 mo) for pembrolizumab vs EXTREME and 68.6 mo (range, 61.2-82.1 mo) for pembrolizumab + chemotherapy vs EXTREME. The 5-year OS rate for pembrolizumab vs EXTREME was, respectively, 19.9% vs 7.4% in CPS ≥20, 15.4% vs 5.5% in CPS ≥1, and 14.4% vs 6.5% in total populations. The 5-year OS rate for pembrolizumab + chemotherapy vs EXTREME was, respectively, 23.9% vs 6.4% in CPS ≥20, 18.2% vs 4.3% in CPS ≥1, and 16.0% vs 5.2% in total populations. 5-yr OS and PFS rates, ORR, and DOR are shown in the table. Grade 3-5 treatment-related AEs were 17.0% for pembrolizumab, 71.7% for pembrolizumab + chemotherapy, and 69.3% for EXTREME. With an extended follow-up of 5 years, first-line pembrolizumab and pembrolizumab + chemotherapy continued to show durable antitumor activity and manageable safety in R/M HNSCC. These results further support pembrolizumab and pembrolizumab + chemotherapy as first-line standard of care in R/M HNSCC.Table: 659MOP vs EP vs EP + C vs EP + C vs EPEP + CECPS ≥20, n1331221261105-yr OS, %19.97.423.96.45-yr PFS, %9.61.29.7-ORR, %23.336.145.238.2DOR, median (range), mo23.4 (2.7-75.5+)4.3 (1.2+- 38.2+)7.1 (2.1+-73.8+)4.2 (1.2+- 38.2+)CPS ≥1, n2572552422355-yr OS, %15.45.518.24.35-yr PFS, %6.02.06.31.0ORR, %19.134.938.035.7DOR, median (range), mo23.4 (1.5+-75.5+)4.5 (1.2+- 73.9+)6.7 (1.6+-73.8+)4.3 (1.2+- 66.5+)Total population, n3013002812785-yr OS, %14.46.516.05.25-yr PFS, %5.11.75.60.8ORR, %16.936.037.036.3DOR, median (range), mo22.6 (1.5+-75.5+)4.5 (1.2+-73.9+)6.7 (1.6+- 73.8+)4.3 (1.2+- 66.5)P, pembro; E, EXTREME; C, chemo Open table in a new tab