2019 ASCO Annual Meeting!
Session: Head and Neck Cancer
Type: Oral Abstract Session
Time: Friday May 31, 2:45 PM to 5:45 PM
Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Head and Neck Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 6000)
Author(s): Danny Rischin, Kevin J. Harrington, Richard Greil, Denis Soulieres, Makoto Tahara, Gilberto de Castro, Amanda Psyrri, Neus Baste, Prakash C. Neupane, Ase Bratland, Thorsten Fuereder, Brett Gordon Maxwell Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Yayan Zhang, Fan Jin, Burak Gumuscu, Barbara Burtness; Peter MacCallum Cancer Centre, Melbourne, Australia; The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust National Institute of Health Research Biomedical Research Centre, London, United Kingdom; Paracelsus Medical University, Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Salzburg, Austria; Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada; National Cancer Center Hospital East, Kashiwa, Japan; Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil; National Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; Vall d’Hebron University Hospital, Barcelona, Spain; University of Kansas Medical Center, Westwood, KS; Oslo University Hospital, Oslo, Norway; Medical University of Vienna, Vienna, Austria; Royal Brisbane and Women's Hospital, Herston and University of Queensland, Queensland, Australia; Catalan Institute of Oncology, Hospitalet de Llobregat, Barcelona, Spain; Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; University Hospital, Zurich, Switzerland; University Malaya, Kuala Lumpur, Malaysia; Merck & Co., Inc., Kenilworth, NJ; Yale University School of Medicine and Yale Cancer Center, New Haven, CT
Background: KEYNOTE-048 is a phase 3 study of P or P + chemo (C) vs EXTREME (E) as 1L therapy for R/M HNSCC (NCT02358031). At the second interim analysis (IA2), P significantly improved OS in the PD-L1 combined positive score (CPS) ≥20 and ≥1 populations and had noninferior OS in the total population with favorable safety; P+C significantly improved OS in the total population with comparable safety. We present the protocol-specified final results. Methods: 882 pts with locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting who provided a tumor sample for PD-L1 testing were randomized to P 200 mg Q3W for 24 mo (n = 301), P for 24 mo + 6 cycles of C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/d for 4 d Q3W) (n = 281), or E (cetuximab 400 mg/m2 loading/250 mg/m2 QW + 6 cycles of chemo) (n = 300). OS superiority was tested sequentially for P+C vs E in the CPS ≥20 population, then the CPS ≥1 population, and for P vs E in the total population (superiority thresholds: one-sided P = .0023, .0026, and .0059, respectively). Data cutoff was 25 Feb 2019 (~25 mo after last pt randomized). Results: P+C significantly improved OS vs E in the CPS ≥20 (HR 0.60, 95% CI 0.45-0.82, P = .0004; median 14.7 vs 11.0 mo) and CPS ≥1 (HR 0.65, 95% CI 0.53-0.80, P< .0001; median 13.6 vs 10.4 mo) populations. HR (95% CI) for PFS was 0.76 (0.58-1.01) for CPS ≥20 and 0.84 (0.69-1.02) for CPS ≥1. ORR (P+C vs E) was 42.9% vs 38.2% for CPS ≥20 and 36.4% vs 35.7% for CPS ≥1; median DOR was 7.1 vs 4.2 mo and 6.7 vs 4.3 mo, respectively. P did not significantly improve OS vs E in the total population (HR 0.83, 95% CI 0.70-0.99, P = .0199; median 11.5 vs 10.7 mo). HR (95% CI) for PFS was 1.29 (1.09-1.53). ORR (P vs E) was 16.9% vs 36.0%; median DOR was 22.6 vs 4.5 mo. All-cause gr 3-5 AE rates were 54.7% for P, 85.1% for P+C, and 83.3% for E. Conclusion: Overall, KEYNOTE-048 showed that compared with E, P+C had superior OS in the PD-L1 CPS ≥20, CPS ≥1, and total populations with comparable safety and P had superior OS in the CPS ≥20 and ≥1 populations, noninferior OS in the total population, and favorable safety. These results support pembrolizumab and pembrolizumab + platinum + 5-FU as new 1L standards of care for R/M HNSCC. Clinical trial information: NCT02358031