279MO Durable immune-mediated survival plateau in metastatic LCNEC after fixed-duration chemo-immunotherapy: Final 4-year analysis of the prospective LANCE study

Background: Large-cell neuroendocrine carcinoma (LCNEC) is a rare, biologically heterogeneous thoracic malignancy with dismal outcomes and no established immunotherapy standard.Prospective data are exceptionally limited.Preliminary findings from the LANCE study (NCT06049966) suggested activity of carboplatinetoposide plus atezolizumab (CT+A).This final 4-year analysis provides the first mature prospective evidence of long-term survivorship with chemo-immunotherapy in metastatic LCNEC.Methods: LANCE is a prospective, real-world observational study enrolling patients with untreated metastatic LCNEC who received first-line CT or CT+A.Overall survival (OS) was the primary endpoint.Kaplan-Meier estimates, log-rank testing, and Cox proportional hazards models were used.A predefined 48-month landmark analysis evaluated durable immune-mediated benefit.Results: Seventeen patients were included.At a median follow-up of 53.4 months, CT+A improved OS (log-rank p=0.051), corresponding to a 66% reduction in mortality risk (HR 0.34; 95% CI 0.11-1.07;p=0.06).A pronounced survival tail emerged: 12-, 24-, 36-and 48-month OS with CT+A were 60%, 40%, 40% and 40%, respectively, versus 14.3%, 14.3%, 0% and 0% with CT.All long-term survivors discontinued atezolizumab after 2 years and remained disease-free off treatment (median treatmentfree interval 30.1 months), supporting durable immune control without continuous therapy.No late immune-related toxicities were observed. Conclusions:This mature 4-year analysis demonstrates a robust and sustained survival plateau after finite-duration chemo-immunotherapy in metastatic LCNEC-an unprecedented finding in prospective data for this disease.The prolonged treatmentfree remission suggests that fixed-duration immunotherapy may achieve deep and durable responses in a biologically selected subset.LANCE provides the first prospective long-term survival evidence in LCNEC and establishes a rationale for biomarker-driven clinical trials aimed at validating durable benefit and refining patient selection.