What question did this study set out to answer?

This research aims to evaluate survival patterns and the impact of immunotherapy in metastatic large-cell neuroendocrine carcinoma.

March 12, 2026Open Access

280P Survival patterns in large-cell neuroendocrine carcinoma: Impact of histology, molecular features, and immunotherapy

Key Points

This research aims to evaluate survival patterns and the impact of immunotherapy in metastatic large-cell neuroendocrine carcinoma.
Conducted a prospective, real-world observational study (LANCE)
Enrolled patients with untreated metastatic LCNEC receiving first-line treatment
Evaluated overall survival as primary endpoint using Kaplan-Meier and Cox models
Performed a 48-month landmark analysis for immune-mediated benefits
CT+A improved overall survival, indicated by a 66% reduction in mortality risk (HR 0.34)
Survival rates at various time points showed 60%, 40%, 40%, and 40% for CT+A compared to 14.3% for CT
All long-term survivors were disease-free after discontinuation of atezolizumab for 2 years
No late immune-related toxicities observed

Abstract

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.

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