8107 Background: Platinum - etoposide with PD-L1 inhibitors is the standard first-line treatment for ES-SCLC. However, real-world outcome data remain limited, particularly regarding the prognostic impact of frequently used concomitant medications. Methods: Retrospective multicenter cohort (9 Spanish centers; Oct 2019 - Apr 2025) of ES-SCLC treated with first-line platinum - etoposide plus anti-PD-L1. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan - Meier. Proton pump inhibitor (PPI), corticosteroid*, and antibiotic use within 30 days before treatment initiation were recorded. Multivariable Cox models were adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS), liver/bone/central nervous system (CNS) metastases (mets), and medications. The immune-related adverse event (irAE) - OS association was explored using time-fixed and 12-week landmark analyses. Results: A total of 442 patients were included (median age 66, 67% male, 90% ECOG PS 0–1); PD-L1 inhibitor: atezolizumab 97%, durvalumab 3%, pembrolizumab <1%. Liver, bone, and CNS mets were present in 40%, 34%, and 27%. PPIs, corticosteroids, and antibiotics were used in 51%, 33%, and 26%. Most (77%) completed induction (4 cycles); 79% initiated maintenance (6% after <4 cycles). ORR was 80% and DCR 90% (n=404 evaluable; routine assessment). With median follow-up of 27.2 months (reverse Kaplan - Meier), median PFS was 5.6 months (95% CI 5.3 - 6.1) and median OS 10.2 months (95% CI 8.4 - 11.3); 12-month OS 43%. On multivariable analysis (complete-case n=415; Table), ECOG PS ≥2 and liver/bone/CNS mets were associated with worse OS, while PPIs, corticosteroids, and antibiotics were not. irAEs occurred in 24%; time-fixed analysis suggested improved OS (adjusted HR 0.61; 95% CI 0.45 - 0.81; p<0.001), but this was not confirmed in 12-week landmark analysis (HR 0.84; 95% CI 0.55 - 1.29; p=0.43). Conclusions: In this large real-world ES-SCLC cohort treated with first-line chemoimmunotherapy, ECOG PS and metastatic burden remained key prognostic factors. Concomitant PPIs, corticosteroids, and antibiotics were not independently associated with OS, although residual confounding by indication cannot be excluded. The irAE - OS association was not confirmed by landmark analysis, highlighting the importance of time-dependent methods. Multivariable Cox regression for OS (n=415). Variable HR (95% CI) p-value ECOG PS ≥2 vs 0-1 1.47 (1.02–2.12) 0.039 Liver mets 1.53 (1.22–1.94) <0.001 Bone mets 1.52 (1.19–1.93) <0.001 CNS mets 1.41 (1.10–1.81) 0.006 PPI (≤30d) 1.13 (0.89–1.44) 0.311 Corticosteroids (≤30d)* 1.03 (0.79–1.33) 0.842 Antibiotics (≤30d) 1.18 (0.89–1.55) 0.245 *Non-prophylactic systemic corticosteroids (≥10 mg/day prednisone-equivalent).
Portu et al. (Thu,) studied this question.