In the phase 3, randomized, open-label KEYNOTE-040 study (NCT02252042), pembrolizumab (pembro), compared with standard of care (SOC), prolonged survival in patients (pts) with recurrent and/or metastatic HNSCC that progressed during or after platinum-based therapy. Post hoc analyses were conducted to evaluate pembro vs SOC by (1) each of 3 SOC choices, (2) prior cetuximab, and (3) second PFS (PFS2; time from randomization to disease progression after initiation of new anticancer therapy).
Eligible pts (N = 495) randomly assigned (1:1) to receive pembro (200 mg every 3 weeks) or investigator choice of methotrexate (40 mg/m2 weekly), docetaxel (75 mg/m2 every 3 weeks), or cetuximab (400 mg/m2 loading dose then 250 mg/m2 weekly). Primary end point: OS; PFS and ORR were secondary end points.
Outcomes for pembro vs each SOC choice are in the table. Regardless of prior cetuximab exposure, survival benefit with pembro was observed. There was a trend toward improved PFS and ORR in those with no prior cetuximab. In pts (N = 210) with no prior cetuximab, median OS was 8.2 vs 6.9 months (mo) for pembro vs SOC (HR 0.78; 95% CI 0.56-1.07; P = 0.062), median PFS was 2.9 vs 2.3 mo (HR 0.84; 95% CI 0.62-1.15; P = 0.135), and ORR was 21.6% vs 13.0% (P = 0.076). In pts (N = 285) who had prior cetuximab, median OS was 8.4 vs 7.1 mo for pembro vs SOC (HR 0.89; 95% CI 0.68-1.16; P = 0.191), median PFS was 2.1 vs 2.3 mo (HR 1.13; 95% CI 0.88-1.46; P = 0.825), and ORR was 9.7% vs 7.9% (P = 0.354). Median PFS2 was 6.6 vs 5.4 mo for pembro vs SOC (HR 0.75; 95% CI 0.62-0.91; P = 0.002).Table: 1047PD
|Pembro n = 247||Methotrexate n = 65||Cetuximab n = 73||Docetaxel n = 110|
|HR, pembro vs SOC (95% CI)||–||0.81 (0.59-1.11)||0.77 (0.57-1.03)||0.81 (0.62-1.05)|
|HR for pembro vs SOC (95% CI)||–||0.95 (0.71-1.27)||0.93 (0.70-1.23)||1.02 (0.79-1.32)|
|Rate at 6 months, %||25.6||21.5||21.9||17.9|
|Difference for pembro vs SOC (95% CI)||–||8.7 (–1.4 to 15.8)||4.5 (–5.4 to 12.0)||3.4 (–5.0 to 10.5)|
The trend was toward improved OS for pembro vs all 3 SOC choices, regardless of prior cetuximab exposure. PFS and ORR were improved in those who had no prior cetuximab, although this may represent a less heavily pretreated population. Pembro, compared with SOC, improved PFS2. Future analyses will evaluate subsequent therapies after initial progression.
Clinical trial identification
NCT02252042; Trial initiated: September 29, 2014.
Legal entity responsible for the study
Merck & Co, Inc.
Merck & Co, Inc.
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co, Inc, Kenilworth, NJ, USA.
C. Le Tourneau: Honorararia: Bristol-Myers Squibb, MSD, Merck Serono, Nanobiotix, Amgen, Roche, Novartis; Travel expenses: Bristol-Myers Squibb, MSD, Merck Serono. E.E.W. Cohen: Consultant: Merck, BMS, AstraZeneca, Human Longevity, Inc, Pfizer, EMD Serono. K.J. Harrington: Honoraria, consultant, and speakers bureau: Amgen, AstraZeneca, Merck, Merck Sharp & Dohme, Pfizer, BMS; Research funding: AstraZeneca, Merck; Travel: Merck Sharp & Dohme. L. Licitra: Consultant: Eisai, Amgen, Boehringer Ingelheim, Debiopharm Group, AstraZeneca, Novartis, Bayer, Merck, Merck Serono, Roche, Bristol-Myers Squibb; Research funding: Eisai, Amgen, Merck Serono, Boehringer Ingelheim, AstraZenca, Novartis, Roche, Merck. M-J. Ahn: Advisory board member: AstraZeneca, Lilly, Lyzz, A. Soria: Personal fees for giving lectures: Bristol-Myers Squibb, Novartis, Roche, all outside the submitted work. J-P. Machiels: Advisory board member: MSD (uncompensated), Debio, Nanobiotix, Innate. R. Mehra: Previous employment spouse: GlaxoSmithKline; Advisory board member: Bayer, Bristol-Myers Squibb, Genentech, InnatePharma, all outside the submitted work. B. Burtness: Advisory board member: Merck, Astra-Zeneca, Bristol-Myers Squibb, Aduro, Amgen, Genentech; Research funding: Merck, Advaxis, Bristol-Myers Squibb; Honoraria: IDDI; Travel, accommodation, expenses: Boehringer Ingelheim. P. Zhang: Employment and travel: Merck. J. Cheng, R. Swaby: Employment and stock: Merck. D. Soulières: Advisory board member and research funding: Merck. All other authors have declared no conflicts of interest.