Chemo-immunotherapy (Chemo-ICI) versus chemotherapy (Chemo) alone as a first-line therapy (1L) in extensive-stage small cell lung cancer (ES-SCLC): An individual patient data (IPD)–based synthetic meta-analysis from randomized control trials (RCTs).

Abstract

e20164 Background: SCLC is an aggressive high-grade neuroendocrine cancer with a high propensity for early metastasis, often leading to extensive disease on presentation. Chemo-ICI has emerged as the standard of care (SOC) for 1L ES-SCLC, though the magnitude of benefit remains uncertain and is variable across RCTs. Here, we estimate the pooled treatment effect on time-to-event outcomes using IPD from trials comparing Chemo-ICI vs. Chemo. Methods: Seven eligible phase II and III RCTs were identified through a literature search using PubMed and EMBASE. Trials (both negative and positive) evaluating first-line anti-PD-1/PD-L1 in combination with Chemo vs. Chemo alone for ES-SCLC were included. All included trials had available Kaplan-Meier (KM) plots for reconstruction of IPD using the IPDfromKM R package. We reconstructed synthetic KM curves and compared progression-free survival (PFS) and overall survival (OS) for IPD using the log-rank test and estimated HRs using the Cox model. All analyses were performed in R v 4.4.1. Results: Of the 3,057 eligible patients, 1,623 received Chemo-ICI, while 1,434 received chemotherapy alone. For PFS, Chemo-ICI showed a higher median PFS of 6.1 months (95% CI: 5.9-6.3) vs. Chemo [5.4 months (95% CI: 5.3-5.5); HR of 0.65 (95% CI: 0.59-0.7; p < 0.0001 )]. At 12 months, the estimated PFS probability was 20.3% in the Chemo-ICI cohort and 6.4% in the Chemo cohort. At 24 months, the estimated PFS probability was 11.6% in the Chemo-ICI cohort and 2.2% in the Chemo cohort. For OS, Chemo-ICI showed a higher median OS of 15.9 months (95%CI: 14.2-16) vs. Chemo of [12.1 months (95%CI: 11.2-12.2); HR of 0.72 (95%CI: 0.66-0.79; p < 0.0001 )]. At 12 months, the estimated OS probability was 62.8% in the Chemo-ICI cohort and 50.2% in the Chemo cohort. At 24 months, the estimated OS probability was 29.1% in the Chemo-ICI cohort and 20.3% in the Chemo cohort. Conclusions: To the best of our knowledge, this is the most comprehensive synthetically generated IPD meta-analysis to date, comparing Chemo-ICI with Chemo alone in the first line setting for ES-SCLC. Our analysis shows that first-line Chemo-ICI provides statistically significant but modest improvements in PFS and OS over chemotherapy alone in ES-SCLC, with durable benefit confined only to a small subset of patients. These findings highlight the need for predictive biomarkers to guide patient selection for first line Chemo-ICI while minimizing toxicity in patients with ES-SCLC.