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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).
Journal article

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).

  • Rischin, Danny Peter MacCallum Cancer Centre, Melbourne, Australia;
  • Harrington, Kevin J. The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust National Institute of Health Research Biomedical Research Centre, London, United Kingdom;
  • Greil, Richard Paracelsus Medical University, Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Salzburg, Austria;
  • Soulieres, Denis Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada;
  • Tahara, Makoto National Cancer Center Hospital East, Kashiwa, Japan;
  • de Castro, Gilberto Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil;
  • Psyrri, Amanda National Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece;
  • Baste, Neus Vall d’Hebron University Hospital, Barcelona, Spain;
  • Neupane, Prakash C. University of Kansas Medical Center, Westwood, KS;
  • Bratland, Ase Oslo University Hospital, Oslo, Norway;
  • Fuereder, Thorsten Medical University of Vienna, Vienna, Austria;
  • Hughes, Brett Gordon Maxwell Royal Brisbane and Women's Hospital, Herston and University of Queensland, Queensland, Australia;
  • Mesia, Ricard Catalan Institute of Oncology, Hospitalet de Llobregat, Barcelona, Spain;
  • Ngamphaiboon, Nuttapong Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;
  • Rordorf, Tamara University Hospital, Zurich, Switzerland;
  • Wan Ishak, Wan Zamaniah University Malaya, Kuala Lumpur, Malaysia;
  • Zhang, Yayan Merck & Co., Inc., Kenilworth, NJ;
  • Jin, Fan Merck & Co., Inc., Kenilworth, NJ;
  • Gumuscu, Burak Merck & Co., Inc., Kenilworth, NJ;
  • Burtness, Barbara Yale University School of Medicine and Yale Cancer Center, New Haven, CT;
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Published in:
  • Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 6000-6000
Cancer Research
Oncology
English 6000 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/208493
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