Evaluation of survival after chemo-immunotherapy in veterans with extensive-stage small cell lung cancer and brain metastases.

Abstract

8110 Background: Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with rapid progression and poor long-term survival. For decades, platinum–etoposide chemotherapy has produced high initial response rates, but relapse is nearly universal. The addition of atezolizumab or durvalumab to first-line chemotherapy is now standard of care based on improved survival in the IMpower133 and CASPIAN trials, with reported OS 12.3 and 13 months, respectively. However, these pivotal trials enrolled highly selected populations and largely excluded patients with active brain metastases, limiting generalizability. Veterans are particularly underrepresented in clinical trials due to comorbidities and performance status, leaving the real-world effectiveness of chemo-immunotherapy and immune biomarkers in this population poorly defined. Methods: We conducted a retrospective cohort study of Veterans with ES-SCLC treated with first-line chemotherapy alone or chemo-immunotherapy within the Veterans Affairs (VA) health system. Overall survival (OS) was assessed using Kaplan–Meier methods and Cox proportional hazards models in propensity-matched cohorts. Prespecified subgroup analyses evaluated whether treatment effects differed by brain metastasis status. Exploratory analyses also assessed the prognostic association between baseline absolute neutrophil-to-lymphocyte ratio (ANC/ALC) and survival. Results: In the matched overall cohort (n = 1,250), chemo-immunotherapy significantly improved OS compared with chemotherapy alone (median OS 8.88 vs 7.44 months; HR 0.75, p < 0.0001). Among patients who received chemo-immunotherapy (n = 625), 87.0% were treated with atezolizumab and 9.6% with durvalumab. For patients with brain metastases at diagnosis (n = 312), chemo-immunotherapy significantly improved survival (median OS 8.76 vs 5.52 months; HR 0.57, p < 0.0001). An elevated pre-treatment absolute neutrophil count (ANC) to absolute lymphocyte count (ALC) ratio > 2.5 was independently associated with worse survival in both chemo-immunotherapy (HR 1.35, p = 0.013) and chemotherapy-only (HR 1.47, p = 0.0004) groups. Conclusions: This study represents the largest real-world cohort of Veterans with ES-SCLC and demonstrates a significant overall survival benefit with chemo-immunotherapy. The benefit was particularly pronounced among patients with brain metastases, a group historically underrepresented in clinical trials. Elevated ANC/ALC was identified as a potential prognostic biomarker associated with poor outcomes regardless of treatment. Notably, overall survival in our Veteran cohort remained substantially lower than in registrational trials, highlighting the urgent need for future studies with broader eligibility criteria that better reflect real-world populations.