Predictors of response to immune checkpoint inhibitors (ICI) rechallenge post-disease progression in solid tumors: A systematic review and meta-analyses.

Abstract

2612 Background: Rechallenge with the same or different ICI has been proposed as a second line option in patients who progress on an initial ICI course. Considering rechallenge risks of limited benefit and further toxicity, identifying predictors for patients benefiting from rechallenge would provide much needed guidance for practice. We present a systematic review and meta-analyses of response predictors to ICI rechallenge after disease progression in solid tumors. Methods: A systematic search of PubMed, Cochrane database and ASCO meeting library was done for studies published up to Jan 2022 evaluating the efficacy of ICI rechallenge in patients with advanced solid tumors after disease progression on initial ICI. Predictors of interest included duration of the initial ICI course using a cutoff point of 6 months, and best overall response (BOR) to initial ICI: stratified into responders (complete or partial response or stable disease) and non-responders (progressive disease). Odds ratios (OR) for ICI rechallenge response were calculated & pooled in reference to initial ICI duration and its BOR using the fixed effects model. ORs with a 95% confidence interval [CI] not overlapping the null value (1) were considered statistically significant. Results: A total of 56 studies reporting on ICI rechallenge upon progression, comprising 3579 patients, of which 31 studies have switched their second ICI regimen. Initial ICI was anti-PD-1 in 37 studies, anti-CTLA-4 in 14 studies, and anti-PD-L1 in 10 studies. Involved solid cancers included melanoma (n = 30), NSCLC (n = 15), RCC (n = 6), and others (n = 5). Pooled objective response rate for rechallenge was 18.4% ([15.4-21.4], I2 = 84.6%), with the highest being among melanoma patients (21.2% [17.2-25.2], I2= 83.4%). For BOR, no significant difference was found for the entire cohort (OR = 1.34 [0.86 - 2.09], I2 = 27.1%). In melanoma studies, response to ICI rechallenge was significantly higher in patients responding to the initial ICI prior to progression (OR = 1.87 [1.03-3.39], I2 = 24.5%). For treatment duration, there was no difference in the entire cohort concerning ICI rechallenge (OR = 1.54 [0.86-2.75], I2 = 14.2%), yet melanoma patients showed a significant difference favoring those who had longer response durations on initial ICI (OR = 2.05 [1.01-4.16], I2 = 0.0%). Conclusions: Response to rechallenge in advanced melanoma patients was more common in initial ICI responders with a longer course duration ( > 6 months). More homogeneous studies are needed to validate our findings and investigate other potential markers for rechallenge such as PD-L1 status & mutational burden. [Table: see text]