Abstract 5464: Predictive biomarkers for PD-1 and PD-L1 checkpoint inhibitor response in NSCLC: An analysis of clinical trial and real-world data

Abstract

Abstract Importance: Largest analysis combining clinical trial and real-world data (RWD) to assess the clinical utility of biomarkers for anti-PD-1/PD-L1 checkpoint inhibitors (CPI) in NSCLC patients. Objective: To assess the association between tumor PD-L1, TMB and blood analytes with clinical outcomes in patients with advanced NSCLC following CPI therapy. Design: Retrospective cohort study with patients stratified into high and low biomarker groups. Correlation with treatment outcome in the different biomarker groups was investigated and compared between patients treated with CPI versus chemotherapy. Setting: Data derived from electronic health records mostly from community oncology settings were combined with clinical trial data. Participants: Starting with 71850 patients with advanced NSCLC who received CPI or chemotherapy, we selected 24152 patients from an electronic health record-derived de-identified NSCLC clinicogenomic database (CGDB) from a real-world cohort and nine Roche atezolizumab trials. Patients were diagnosed between January 2011 and February 2020 (data collection cut-off date). Main Outcomes and Measures: Drug response was assessed by RECIST criteria for clinical trials and real-world response for RWD. Durable response was defined as having CR/PR without progression during the study period of 270 days. Associations of biomarker levels with treatment outcomes were analyzed using Fisher’s exact test. Results: High expression of PD-L1 on tumors (≥50%) were associated with lower risk of resistance to CPI (odds ratio [OR] 0.21; 95% CI = 0.14, 0.32; P< .001). The association was stronger in patients who had prior chemotherapy than first line CPI, with non-squamous than squamous histology, and smokers than non-smokers. Higher TMB (≥9.57 mut/Mb) was also associated with durable response (OR = 0.41; CI = 0.30, 0.55; P< .001). The combination of high TMB and PD-L1 expression was the strongest predictor of durable response (OR = 0.04; CI = 0.00, 0.20; P< .001). There was no evidence of an association between PD-L1/TMB and response to chemotherapy, suggesting a CPI-specific predictive effect. In contrast, blood analytes were prognostic, having correlation with clinical outcome irrespective of treatment type. Conclusion: This study supports the predictive utility of PD-L1 expression and TMB for NSCLC patients receiving CPI therapy and further elucidates their utility in patient sub-populations. Citation Format: WeiQing Venus So, David Dejardin, Eva Rossmann, Jehad Charo. Predictive biomarkers for PD-1 and PD-L1 checkpoint inhibitor response in NSCLC: An analysis of clinical trial and real-world data. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5464.