Tumour mutational burden in treatment-resistant tumours – Authors' reply

[...]they suggest the potential for non-linear relationships between tTMB and overall survival in patients with non-small-cell lung cancer (NSCLC). [...]studies assessing the predictive value of tTMB for overall survival among patients with advanced or metastatic NSCLC receiving pembrolizumab monotherapy have not reported such non-linear associations.4 Furthermore, with the inclusion of patients with ten distinct cancer types in our analysis (none with NSCLC) from a single-arm study design with various numbers and disparate types of previous and subsequent standard therapies and different survival prognosis across tumour types, it seems unlikely that using multiple tTMB groups would have provided greater ability to identify an association between overall survival and tTMB than the analysis we used. AM reports research funding to their institution during the conduct of this study from Merck Sharp & Dohme (MSD); research grants to their institution for other clinical trials or pre-clinical studies from MSD, Bristol-Myers Squibb, AstraZeneca, Roche/Genentech, Pfizer, and Sanofi; a research grant from MSD Avenir Foundation (France); honoraria for serving as a scientific advisory board member for MSD, AstraZeneca, Roche/Genentech, and Pfizer; honoraria for serving as a symposium scientific committee member or speaker for Bristol-Myers Squibb and Roche/Genentech; travel expenses from MSD, Bristol-Myers Squibb, AstraZeneca, and Roche/Genentech; additional research funding or study drug supply from MSD, Bristol-Myers Squibb, AstraZeneca, and Roche/Genentech; and consulting fees from Sanofi.