Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: Analysis of Number Needed To Treat and Number Needed To Harm

Purpose: Nivolumab, a programmed cell death protein (PD)-1 inhibitor, was approved by the US Food and Drug Administration in 2021 advanced/metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, in combination with fluoropyrimidine and platinum-based chemotherapy. In the present study, the number needed to treat (NNT) for overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) -and the number needed to harm (NNH) for tolerability outcomes -with nivolumab + chemotherapy versus chemotherapy alone were determined.Methods: NNT and NNH were calculated as the reciprocal of the risk difference between the two treatment arms, with the 95% CIs calculated as the reciprocals of the upper and lower bounds of the 95% CI of the risk difference, using data from the CheckMate 649 study.Findings: Among all treated patients, the NNTs for OS over 1 and 2 years were 15.15 and 12.05; for PFS, 10.87 and 19.61; and for ORR over the entire trial period, 8.95. The corresponding NNTs in the subgroup with PD-L1 CPS >= 5 were less. The NNH for grade >= 3 treatment-related adverse events (TEAEs) over 1 year among all treated patients was 7.02.Implications: The small estimated NNT values in this study suggest that patients would benefit from nivolumab + chemotherapy, and while the NNH for grade >= 3 TRAEs was small, the NNH for any individual TRAE were large or negative.