Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)
- PMID: 30944020
- PMCID: PMC6446400
- DOI: 10.1186/s40425-019-0578-0
Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)
Abstract
Two phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51-0.96; p = 0.01) and HR of 0.80 (95%CI 0.65-0.98, p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or methotrexate). The gain in OS was similar in both studies, underscoring the role of anti-PD1 drugs in R/M HNSCC patients. One of the striking discrepancies between CheckMate 141 and KEYNOTE 040 was the OS observed in the control SOC arms (6.9 months median in KEYNOTE 040 versus 5.1 months in CheckMate 141), which inadvertently set a higher threshold in the bio-statistical analysis of KEYNOTE 040 so that the clinical outcome of every patient was influential in the analysis. We perform a comparative analysis of the two studies to identify potential factors in the control arm that can impact clinical trial bio-statistical outcomes and which may have implications for future immunotherapy clinical trial designs.
Trial registration: ClinicalTrials.gov NCT02105636 NCT02252042.
Keywords: Anti-PD-1 therapy; Clinical trials; Head and neck squamous cell carcinoma; Immune checkpoint therapy; Immunotherapy.
Conflict of interest statement
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Competing interests
Dr. P. Bruzzi served on advisory boards for MSD, Astrazeneca, and Pfizer, and received honoraria for lectures and educational events from BMS, Sanofi, Merck Serono. Novartis, Ipsen, Eisai, MSD, Pierre Fabre, and Amgen. Dr. Faivre is consultant and has participated in research funded by BeiGene, Blueprint Medicine, Bristol-Myers Squibb, Bayer Pharma, Eli Lilly, Incyte, Ipsen, Merck Serono, MSD, and Novartis. Dr. Giglio is member of the advisory board of Merck and MSD. He is participating as PI in clinical trials sponsored by BMS, MSD and ICON and has received honoraria for lectures from Merck, MSD and BMS. Dr. Grünwald receives research support from AstraZeneca, Pfizer, MSD and BMS. Dr. Grünwald serves on advisory boards for AstraZeneca, Pfizer, MSD, BMS, Merck Serono, Novartis, Ipsen, Roche, EUSA Pharma and has received honoraria for lectures from AstraZeneca, Pfizer, MSD, Roche, Ipsen, Eisai, Merck Serono and BMS. Dr. Leemans is a member of the advisory board of Merck Serono and MSD, serves as PI in a clinical trial sponsored by BMS, and has received honoraria for lectures from Merck Serono. Dr. Licitra is a member of the advisory board of Merck Serono, DEBIO, Norgine, Astrazeneca, MSD, BMS, Eisai and received research grant from Boehringer, Eisai, Jannsen. Dr. Machiels is a member of the advisory board of INNATE, DEBIO, Nanobiotix, Astrazeneca, MSD (uncompensated) and received research grant from Janssen, Novartis, Bayer. Dr. Pai receives research support from Abbvie, Astrazeneca/MedImmune, Cue, and Tesaro and serves on advisory boards for Abbvie, Astrazeneca/MedImmune, Cue, and Merck. Dr. Seiwert has received honoraria from Aduro Biotech, Astra Zeneca, Bayer, BMS, Celgene, Innate, Loxo Oncology, Merck, Nanobiotix. Dr. Soulieres serves on the advisory boards for Merck, BMS, Astrazeneca, Pfizer, Novartis, Ipsen, and Eisai. Dr. Vermorken is a member of the advisory board of Merck Serono, Debiopharm, Innate Pharma, PCI Biotech, Synthon Biopharmaceuticals, MSD and received honoraria for lectures from BMS, Sanofi and Merck Serono.
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