Oladimeji Akinboro, Jonathon Joseph Vallejo, Pallavi Shruti Mishra-Kalyani, Erin A. Larkins, Nicole Lauren Drezner, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Harpreet Singh; U.S. Food and Drug Administration, Silver Spring, MD

Background: IO + chemotherapy ± anti-angiogenics comprise FDA-approved 1L regimens for metastatic NSCLC, with IO-only therapy approved only for PD-L1-positive NSCLC. Patients with PD-L1 scores 1- 49% have many therapeutic options, and little is known about how subgroups of patients experience benefit across treatment regimens.

Methods: Data was pooled from 8 randomized controlled trials investigating anti-PD-(L)1 therapy as IO-only or in chemo-IO regimens for the 1L treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay, and analysis was conducted for patients whose tumors had PD-L1 score 1-49%. Tumor-infiltrating immune cell staining was not considered. OS and PFS were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan-Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial and adjusted for age, sex, race, ECOG, histology and smoking status.

Results: A total of 2108 patients with NSCLC and PD-L1 score 1- 49% were identified for this analysis. Baseline characteristics were: 37% aged 65-74 years and 12% aged $75; 67% male; 79% white; 65% ECOG $ 1; and 85% smokers. Median follow-up was 12.1 months. This pooled analysis showed that patients receiving chemo-IO (N=639) had longer PFS and OS compared to patients treated with IO alone (N=529), with median PFS 7.7 vs 4.2 months (HR 0.60; 95% CI 0.48, 0.76) and median OS 21.4 vs 14.5 months (HR 0.68; 95% CI 0.52, 0.90). All results presented are considered exploratory and hypothesis generating.

Conclusions:This exploratory pooled analysis suggests that chemo-IO may improve efficacy outcomes over IO alone in most subgroups of patients with advanced NSCLC with PD-L1 score 1-49%. Patients 75 and over experienced similar outcomes across therapeutic options. Research Sponsor: None.