PIK3 mutation as a predictor of immune checkpoint inhibitor response.

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e15257 Background: Although several biomarkers predicting response to immune checkpoint inhibitor (ICI) therapy have been evaluated, the emerging data is conflicting. There is a lack of real-world data that might help identify biomarkers in diverse populations. Methods: Patients with solid tumors who received ICI and underwent tumor tissue next generation sequencing (NGS) in our institution between 2016-2019 were included in the study. Response to ICI was assessed based on RECIST 1.1 and median progression free survival (mPFS), radiologic response and immune-related adverse events (IRAEs) were analyzed in relation to various molecular biomarkers. Results: 69 patients had complete NGS and RECIST 1.1 data required for analysis. Study cohort included 14 different cancer types. 78% of the patients were smokers. TP53 (62%), CDKN2A (44%), NOTCH1/2 and PIK3 (33%) were the most common mutations identified. 42% patients had CR/PR with ICI and mPFS was 38 weeks (w). A statistically significant improvement in PFS was observed in patients with PIK3 mutated cancers (mPFS 123 weeks vs. 23 weeks, p = 0.012). These patients also had a higher percentage of response (60.9% vs 39.1%, p = 0.5), and were also associated with increased risk of immune related adverse events (IRAEs) (73.9% vs. 37%, p = 0.004). PIK3 mutation had no association with PDL1 status or tumor mutational burden (TMB). Mean TMB was 12.59, and 29% patients had positive PDL1 expression. There was significant difference in mPFS between high (≥20mut/Mb) and low/intermediate TMB (0-19mut/Mb) (mPFS 18w vs. 65 w, p = 0.049) as well as PDL1 positive and negative tumors (40w vs. 18w, p = 0.059). BRAF mutation was associated with early progression in all cancers (mPFS 17w vs 39w, p = 0.033). Conclusions: Conventionally, a marker of poor survival and chemotherapy response, PIK3 mutation was associated with positive ICI response in our study. High incidence of IRAEs in PIK3 mutants also point towards increased ICI activity. High TMB, as expected was associated with ICI response.