Outcomes of anti–PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non–small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: FDA pooled analysis.

9000 Background: FDA-approved 1L treatment options for patients with PD-L1-high advanced NSCLC (PD-L1 score ≥50%) include IO ± chemo (± anti-angiogenics) but it is unclear if chemo substantially improves efficacy outcomes when added to IO in this patient population. Methods: Data was pooled from 12 randomized controlled trials that investigated anti-PD-(L)1 regimens ± chemo 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 with tumor PD-L1 score ≥50%. OS, PFS, and ORR 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; odds ratios were estimated using a logistic regression model with trial as a covariate. All analyses were adjusted for age, sex, race, ECOG, histology and smoking status. Results: A total of 3,189 patients with NSCLC and PD-L1 score ≥50% were identified for this analysis. Baseline characteristics were: 38% ages 65-74 years and 11% ages ≥75 years; 69% male; 80% White; 66% ECOG ≥1; and 89% former/current smokers. Median OS in the pooled chemo-IO ( N= 455) and IO-only ( N= 1,298) arms was 25.0 vs 20.9 months (HR 0.82; 95% CI: 0.62, 1.08); median PFS was 9.6 vs 7.1 months, respectively (HR 0.69; 95% CI: 0.55, 0.87). ORR was higher with chemo-IO than with IO alone (61% vs 43%; Odds ratio 1.2, 95% CI: 1.1, 1.3). Conclusions: This exploratory, hypothesis-generating pooled analysis suggests that most subgroups of patients with advanced NSCLC with PD-L1 score ≥50% receiving FDA-approved chemo-IO regimens may have OS and PFS outcomes that are comparable with or better than IO-only regimens. Patients ≥75 years of age receiving chemo-IO may not have improved outcomes over IO. These results support shared decision-making that balances potential benefits and risks of adding chemo to IO regimens based on patient factors that may impact tolerability. Efficacy outcomes of chemo-IO versus IO alone by subgroup. Subgroup N 1 OS PFS ORR Median, months HR (95% CI) Median, months HR (95% CI) % Odds ratio (95% CI) Age, years <65 898 25.0 vs 23.3 0.67 (0.46, 0.99) 9.4 vs 7.7 0.54 (0.39, 0.75) 62 vs 43 2.2 (1.3, 3.7) 65-74 642 22.2 vs 18.6 0.83 (0.54, 1.28) 9.7 vs 6.8 0.80 (0.56, 1.13) 62 vs 43 1.9 (1.1, 3.4) ≥75 185 NE vs 18.9 1.68 (0.69, 4.06) 11.8 vs 7.2 1.22 (0.58, 2.57) 52 vs 45 1.2 (0.4, 3.8) ECOG 0 602 NE vs 31.8 0.70 (0.40, 1.21) 13.7 vs 8.5 0.61 (0.40, 0.92) 66 vs 47 2.6 (1.5, 4.7) 1+ 1148 17.7 vs 18.0 0.87 (0.64, 1.19) 8.2 vs 6.3 0.75 (0.57, 0.98) 58 vs 41 1.7 (1.1, 2.6) Smoking Never 197 NE vs 14.4 0.39 (0.15, 0.98) 10.2 vs 3.7 0.46 (0.23, 0.92) 69 vs 28 4.6 (1.5, 14.5) Ever 1549 23.0 vs 22.1 0.92 (0.69, 1.22) 9.3 vs 8.2 0.75 (0.59, 0.95) 60 vs 45 1.7 (1.2, 2.5) 1 Patients in the pooled chemo-IO and IO-only arms.