Immune-related adverse event severity and clinical outcomes with immune checkpoint inhibitor immunotherapy in participants with non–small cell lung cancer: Analysis of the lung MAP sub-studies S1400A, S1400I, S1400F, and S1800A.

Abstract

8572 Background: Immune checkpoint inhibitors (ICIs) have advanced the treatment paradigm for non-small cell lung cancer (NSCLC), but ICIs are associated with risk of immune-related adverse events (irAEs). There is an unmet need to better understand how the severity of irAE impacts the clinical outcome of NSCLC treated with ICIs. We hypothesized that participants (pts) with lower grade irAEs would have better outcomes than those with higher grade irAEs and those without irAEs. Methods: We evaluated outcomes in Lung-MAP pts with advanced NSCLC treated with ICIs in the 2L setting (S1400A [durvalumab vs docetaxel], S1400I [nivolumab +/- ipilimumab], S1400F [durvalumab + tremelimumab], and S1800A [pembrolizumab + ramucirumab vs standard-of-care]), using 6-, 12-, and 24-week landmark analyses of the relationship between irAE severity (Grade(G) 1 or 2 vs G3 or 4 and vs no irAE) and overall survival (OS) from the landmark timepoint. OS was compared between groups using Cox Proportional hazards model with separate analyses for ICI-naïve (S1400A and S1400I) and ICI-exposed (S1400F and S1800A). Results: Analyses included 315 ICI-naïve and 127 ICI-refractory pts. In the ICI- naïve cohort, no irAEs and G 3-4 irAEs were associated with inferior OS compared with G1-2 irAEs by 12 wks of treatment (no irAEs: HR 1.68, CI 1.28 – 2.22, p < 0.0005 G3-4: HR 2.28, CI 1.47 – 3.53; p < 0.0005). This difference in OS between the irAE groups was consistent at the 6 wk (p = 0.006) and 24 wk (p = 0.03) landmark timepoints. See table for outcomes in the ICI naïve cohort. In the ICI-exposed cohort, there was no difference in OS between the irAE groups at any landmark timepoint (6 weeks: p = 0.39; 24 weeks: p = 0.98). Conclusions: In the ICI-naïve cohort, G1-2 irAEs in were associated with better OS compared to no irAEs and G3-4 irAEs for all landmark times. This association was not observed in the ICI-exposed cohort. Additional analyses will incorporate molecular and immune features evaluating risk and severity of irAEs. Outcomes for ICI naïve cohort. Landmark Time irAE Group N mOS (95% CI) 6 weeks No irAE 160 9.0 (7.9-10.9) G 1-2 124 14.6 (10.1-19.0) G 3-4 20 5.9 (3.5-10.8) 12 weeks No irAE 124 8.2 (6.5-9.8) G 1-2 130 15.4 (11.5-9.8) G 3-4 29 5.3 (2.9 - 8.0) 24 weeks No irAE 77 7.0 (5.8-9.8) G 1-2 121 14.9 (10.9-18.5) G 3-4 34 5.9 (3.1-13.9)