The interaction of immune checkpoint inhibitor plus chemotherapy in non-small-cell lung cancer: subadditivity, additivity or synergism?

The hypothesis that the interaction of chemotherapy and immune checkpoint inhibitors (ICIs) is synergistic has not been formally validated. The frontline ICI Phase II/III trials in advanced non-small-cell lung cancer were reviewed for the objective response rates (ORRs) and grade 3-5 adverse events (AEs) of ICI-chemotherapy combinations and those of each individual drug. The expected ORR and grade 3-5 AE of ICI-chemotherapy combinations were computed as the arithmetic sum of the pooled effects of each drug. Statistical pooling was performed using a double arcsine transformation and a random-effects model. Our findings suggest an enhanced effect that is less than additive for the ICI-chemotherapy combinations since the actual ORR and grade 3-5 AE were found to be less than the expected additive effect.