There are few treatment options in recurrent/metastatic (R/M) HNSCC after progression on platinum and cetuximab, and their efficacy is disappointing. During KEYNOTE-012, pembrolizumab, an anti–PD-1 antibody that blocks the interaction between PD-1 and its ligands, showed promising antitumor activity in R/M HNSCC. The efficacy and safety of pembrolizumab in patients with R/M HNSCC after progression on platinum and cetuximab are being investigated in the phase 2, nonrandomized KEYNOTE-055 (NCT02255097) study.
Pts receive pembrolizumab 200 mg every 3 weeks. Key eligibility criteria include R/M HNSCC resistant to platinum and cetuximab therapies, measurable disease, and ECOG PS 0-1. Primary outcomes include overall response rate (ORR, RECIST v1.1 by central imaging vendor) performed every 6-9 wk and safety. Adverse events (AEs) were graded using CTCAE, v4.0.
Of the 171 pts who received ≥1 dose of pembrolizumab, median age was 61 y, 81% were male, 75% had ≥2 prior lines of therapy for metastatic disease. As of Jan 29, 2016, median follow-up time was 4 mo (range, 0-14). Treatment-related AEs (TRAEs) occurred in 102 (60%) pts, with 20 (12%) pts experiencing a grade 3-5 TRAE. 4 (2%) pts discontinued and 1 (1%) pt died because of a TRAE. AEs of special immunologic interest occurred in 35 (20%) pts; hypothyroidism (n = 23; grade 1 or 2) and pneumonitis (n = 3, grade 1 or 2; n = 1, grade 3; n = 1, grade 5) were the most common. When confirmed responses were evaluated, the ORR was 15% (PR, n = 25; 95% CI, 10%-21%) with a median duration of response of 7 mo (range, 0-8+); the stable disease rate was 22% (n = 37; 95% CI, 16%-29%). When unconfirmed and confirmed responses were evaluated, the ORR was 22% (CR, n = 2; PR, n = 35; 95% CI, 16%-29%) and the stable disease rate was 15% (n = 25; 95% CI, 10%-21%).
The clinically significant antitumor activity and safety profile of pembrolizumab in heavily pretreated R/M HNSCC shown here confirm findings from KEYNOTE-012 and support ongoing phase 3 trials in head and neck cancer. Further analyses of biomarker data including immunohistochemistry (PD-L1/PD-L2) and interferon gamma gene signatures will be presented.
Clinical trial identification
Legal entity responsible for the study
Merck and Co., Inc.
Merck and Co., Inc.
T. Seiwert: Honoraria: Merck/MSD, Amgen, BMS, Astra Zeneca, Celgene, Serono. D.G. Pfister: Research funding: Merck, Exelixis, Medimmune, Astra Zeneca, Novartis Consulting or Advisory role: Boerhringer Ingelheim - Data Safety Monitoring Committee. S.V. Liu: Consulting Or Advisory Role: Genentech, Boehringer Ingleheim, Caris Life Sciences. J. Gilbert: Research Funding: AstraZeneca (Local PI), Merck, BMS, Steering Committee (unfunded). A. Sukari: Research funding: AstraZenca (PI), Merck (PI), MedImmune (PI), Karyopharm (PI), Boehringer Ingelheim (PI), VentiRx (PI), Mallinckrodt, Inc (PI), Acceleron Pharma (PI), Lilly (PI) Speakers Bureau: Novartis Oncology. E. Massarelli: Research funding: Merck, Bristol Myers Squibb, AstraZeneca, Medimmune Honoraria: Nektar Therapeutics Consulting or Advisory role: Nektar Therapeutics. S. Powell: Research Funding: Boerhringer Ingelheim - Data Safety Monitoring Committee. A. Meister, X. Shu, J. Cheng: Employee of Merck and Co, Inc. J. Bauml: Research funding: BMS, Merck, Astra Zeneca, Celgene,Venti-Rx Consulting or Advisory role: BMS, Merck, Celgene, Eisai. All other authors have declared no conflicts of interest.