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).
Sara I PaiSandrine FaivreLisa LicitraJean-Pascal MachielsJan B VermorkenPaolo BruzziViktor GruenwaldRaul E GiglioC René LeemansTanguy Y SeiwertDenis SoulieresPublished in: Journal for immunotherapy of cancer (2019)
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.
Keyphrases
- clinical trial
- phase iii
- phase ii
- end stage renal disease
- ejection fraction
- newly diagnosed
- prognostic factors
- chronic kidney disease
- healthcare
- randomized controlled trial
- low dose
- type diabetes
- study protocol
- high dose
- small cell lung cancer
- stem cells
- double blind
- mesenchymal stem cells
- chronic pain
- combination therapy
- metabolic syndrome
- photodynamic therapy
- patient reported outcomes
- advanced non small cell lung cancer
- locally advanced
- radiation therapy
- bone marrow
- replacement therapy
- pain management
- current status
- light emitting