Comparison by immunotherapy agent of real-world outcomes with chemoimmunotherapy in first-line extensive-stage small cell lung cancer.

Abstract

8103 Background: Chemoimmunotherapy became the standard of care for extensive-stage small cell lung cancer (ES-SCLC) after two Phase III trials (IMpower133, CASPIAN) demonstrated significant improvement in overall survival (OS) over platinum-based chemotherapy. While both anti-PD-L1 agents provide durable responses in a subset (~10%), the magnitude of benefit with immunotherapy (IO) is similar, suggestive of therapeutic interchangeability. Real-world data (RWD) suggests durvalumab confers superior outcomes in ES-SCLC, compared to atezolizumab. Recently, durvalumab received regulatory approval for limited-stage SCLC, whereas atezolizumab failed to demonstrate benefit after chemoradiation. Here, we investigate whether IO choice impacts outcomes for first-line ES-SCLC. Methods: We retrospectively reviewed the charts of patients diagnosed with ES-SCLC in the Indiana University (IU) Health System from 2018 to 2024. Patients were stratified by receipt of either atezolizumab or durvalumab for first-line chemoIO for comparison of demographics and outcomes. Kaplan-Meier, univariate Cox regression, and Fishers exact test was applied. Results: We identified 158 patients diagnosed with ES-SCLC who received chemoIO (Table 1). Platinum-sensitivity and objective response rates were similar between groups ( P = 0.14 and P >0.9, respectively). The median number of IO cycles received (induction and maintenance) was significant higher with atezolizumab (9), compared to durvalumab (7, P <0.001). Similarly, median progression-free survival (PFS) trended in favor of atezolizumab over durvalumab (6.3 vs 5.2 months, P = 0.08). Subsequent therapy post-progression was comparable between groups, including lurbinectedin (31% vs 23%, P = 0.5) and tarlatamab (17% vs 23%, P = 0.4). The unadjusted median OS for atezolizumab was 16.5 months (95% CI, 13.2-19.5), compared to durvalumab 12.4 months (95% CI, 9.9-17.3) ( P = 0.11). To account for group imbalances, overlap-weighted multivariable Cox regression was performed, in which ECOG performance status (PS) of 0-1 (HR 0.53, 95% CI, 0.30-0.92, P = 0.03) and receipt of atezolizumab (HR 0.56, 95% CI, 0.34-0.93, P = 0.02) were independently associated with improved OS. Conclusions: In our study, atezolizumab demonstrated improved OS and trended to improve PFS in first-line ES-SCLC, compared to durvalumab. Potential confounders when evaluating the impact of IO agents across RWD studies include ECOG PS, variable use of thoracic radiotherapy, geographical differences, and ethnic distributions. Characteristic Atezolizumab (n = 127) Durvalumab (n = 31) Overall (n = 158) P value Age (Q1, Q3) 66 (61, 73) 68 (63, 73) 67 (61, 73) >0.9 Sex (female) 79 (62%) 17 (55%) 96 (61%) 0.5 ECOG PS (0-1) 87 (74%) 20 (69%) 107 (73%) 0.6