1047PDPembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC): Post hoc analyses of treatment options from the phase III KEYNOTE-040 trial

Background: 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). Methods: 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. Results: 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: 1047PDPembro n = 247Methotrexate n = 65Cetuximab n = 73Docetaxel n = 110OSMedian, mo8.46.07.17.7HR, pembro vs SOC (95% CI)–0.81 (0.59-1.11)0.77 (0.57-1.03)0.81 (0.62-1.05)P value–0.0940.0380.058PFSMedian, mo2.12.22.12.5HR for pembro vs SOC (95% CI)–0.95 (0.71-1.27)0.93 (0.70-1.23)1.02 (0.79-1.32)P value–0.3520.2990.557Rate at 6 months, %25.621.521.917.9ORRORR, %14.66.211.011.8Difference 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)P value–0.0400.1630.202 Open table in a new tab Conclusions: 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. Editorial acknowledgement: 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. Legal entity responsible for the study: Merck & Co, Inc. Funding: Merck & Co, Inc. Disclosure: 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.