Tumor proportion score (TPS) and response to first-line (1L) anti–PD-1/PD-L1 plus chemotherapy for metastatic non-small cell lung cancer (NSCLC): A real-world cohort study.

Abstract

e20606 Background: The efficacy of chemotherapy combined with PD-1/PD-L1 inhibitors (CIO) in metastatic NSCLC is influenced by PD-L1 expression levels. Despite this, patients (pts) are often dichotomized as either PD-L1–positive or –negative in clinical practice, and the definitions are not standardized. This retrospective real-world cohort study sought to characterize the clinical outcome after 1L CIO in pts with metastatic NSCLC, as a function of PD-L1 TPS, to develop contemporary benchmarks for timing of intervention when designing 2L therapeutic trials. Methods: This is a retrospective cohort study using the Tempus oncology database. Records were included for pts with NSCLC who had been treated with 1L CIO for metastatic disease from 2017 to 2023 at US centers. Records included valid TPS within 60 days of therapy start, no evidence of ALK , EGFR , or ROS1 mutations, and no evidence of treatment with tyrosine kinase inhibitors. Real-world progression-free survival (rwPFS), overall survival (rwOS), and best overall response (rwBOR) were calculated, and descriptive statistics were used to describe outcomes.Analysis was conducted using the InovaMine platform. Results: Records for 2100 pts were interrogated to identify 880 pts who met our inclusion criteria (TPS=0, 26.6%; TPS=1, 22.3%; TPS >1 to ≤5, 8.4%; TPS >5 to ≤20, 11.6%; TPS >20 to ≤49, 7.3%; TPS ≥50, 23.9%). Pts with TPS=0 or 1 had similar median (95% CI) rwPFS (6.02 mo [5.46–7.59] vs 6.38 mo [5.0–7.4]) and rwOS (14.7 mo [12.7–17.9] vs 18.9 mo [14.2–23.5]); these pts were combined into one TPS ≤1 group. Higher TPS correlated with better rwPFS and rwOS outcomes (Table). Multivariate Cox regression models for rwPFS and rwOS adjusted for age, gender, histology, time to treatment, stage, and ECOG performance status demonstrated that pts with TPS ≤1 had significantly higher hazards compared with those with TPS >1 (Table). Among pts with complete or partial response as rwBOR, a higher proportion had responded within the first 3 mo in TPS ≤1 versus TPS >1 (Table). Conclusions: These results underscore the prognostic value of TPS in metastatic NSCLC treated with 1L CIO. Pts with TPS ≤1 demonstrated significantly worse survival outcomes compared with those with TPS >1, emphasizing the high unmet need for alternative therapeutic strategies in these pts. Objective responses to CIO, although less likely, were established earlier in pts with TPS ≤1 compared to those with TPS >1. Pts without a response to CIO at 3 mo may derive greater benefit from early institution of effective 2L therapy options. TPS ≤1(N=430) TPS >1(N=450) Hazard ratio(95% CI) P value rwPFS, mo 6.0 10.9 1.49(1.19–1.85)* <0.001 rwOS, mo 15.9 22.9 1.34(1.03–1.74)* 0.02 rwBOR CR or PR, % (95% CI) † 39.5(34.8–44.3) 52.4(47.7–57.1) NA - Response achieved within 3 mo, % (95% CI) † 80.0(73.1–85.7) 68.0(61.4–73.7) NA - *Reference: TPS >1. † Non-adjusted.