KEYNOTE-048: Phase 3 study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)
Date | 22 October 2018 |
Event | ESMO 2018 Congress |
Session | Presidential Symposium 3 |
Topics | Immunotherapy Head and Neck Cancers |
Presenter | Barbara Burtness |
Authors |
B. Burtness1, K.J. Harrington2, R. Greil3, D. Soulières4, M. Tahara5, G. De Castro Jr.6, A. Psyrri7, N. Baste Rotllan8, P.C. Neupane9, Å. Bratland10, T. Fuereder11, B.G.M. Hughes12, R. Mesia13, N. Ngamphaiboon14, T. Rordorf15, W.Z. Wan Ishak16, A. Roy17, J. Cheng18, F. Jin19, D. Rischin20
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Abstract
Background
KEYNOTE-048 was an open-label, randomized phase 3 study of P or P + chemotherapy (C) vs EXTREME (E) as first-line systemic therapy for R/M HNSCC (NCT02358031).
Methods
Patients (pts) with R/M HNSCC not curable by local therapy and with no prior systemic therapy (R/M setting) who provided a tumor sample for PD-L1 testing were randomized to P 200 mg Q3W, P + C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/d for 4 d Q3W), or E (cetuximab 400 mg/m2 loading/250 mg/m2 QW + C) given until PD, unacceptable toxicity, 6 cycles (C), or 24 mo (P). Primary end points for P vs E and P + C vs E were PFS and OS in the PD-L1 combined positive score (CPS) ≥20 and ≥1 and total populations (pop). Cutoff date for this final PFS/interim OS analysis was Jun 13, 2018 (minimum follow-up, ~17 mo).
Results
882 pts were randomized: 301 to P, 281 to P + C, 300 to E. P was superior to E for OS in CPS ≥20 (N = 255; median 14.9 vs 10.7 mo; HR 0.61 [95% CI 0.45-0.83]; P = 0.0007) and ≥1 (N = 512; median 12.3 vs 10.3 mo; HR 0.78 [95% CI 0.64-0.96]; P = 0.0086); OS for P was non-inferior to E in the total pop (N = 601). P did not prolong PFS in CPS ≥20 (P = 0.5); per the analysis plan, no further PFS testing was done for P vs E. Confirmed ORR (P vs E) was 23% vs 36% for CPS ≥20, 19% vs 35% for CPS ≥1, and 17% vs 36% for the total pop; median DOR was 20.9 vs 4.2 mo, 20.9 vs 4.5 mo, and 20.9 vs 4.5 mo. Gr 3-5 drug-related AE rates were 17% (P) vs 69% (E). P + C was non-inferior and superior to E for OS in the total pop (N = 559; median 13.0 vs 10.7 mo; HR 0.77 [95% CI 0.63-0.93]; P = 0.0034); OS for P + C was not significantly superior to E in CPS ≥20 and ≥1 at this interim analysis. PFS was not prolonged with P + C (P = 0.2). For P + C vs E, confirmed ORR was 36% vs 36%, median DOR was 6.7 vs 4.3 mo, and gr 3-5 drug-related AE rates were 71% vs 69%.
Conclusions
For first-line R/M HNSCC, P significantly improved OS over E in the PD-L1 CPS ≥20 and ≥1 populations and was noninferior in the total population with favorable safety. P + C significantly improved OS in the total population with safety comparable to E. P and P + C responses were durable. These data support pembrolizumab and pembrolizumab + platinum + 5-FU as new first-line standards of care for R/M HNSCC. The study continues to the final OS analysis.
Clinical trial identification
NCT02358031: Trial initiation, February 6, 2015
Editorial Acknowledgement
Medical writing and editorial assistance was provided by Melanie Leiby, an employee of Merck & Co., Inc., Kenilworth, NJ, USA.