Brief Report: Proposed Clinical Trial Guidelines Based on Clinicopathologic Heterogeneity of Metastatic Pulmonary...

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine carcinoma with clinical and molecular heterogeneity distinct from SCLC. This large retrospective series seeks to define the clinical outcomes for patients with newly diagnosed metastatic LCNEC and whether aligning treatment based on molecular classification improves outcomes.

Clinicopathologic data included demographics, treatment history, and immunohistochemical and genomic results. Patients with suspected transformed LCNEC (tLCNEC) underwent curated pathology review. Patient outcomes were assessed using Kaplan-Meier methodology.

A total of 137 patients were included (100 with pure LCNEC and 37 with mixed histologies), of whom 15 had tLCNEC. For the 115 cases with genomic data available, 63 (55%) were classified as NSCLC like and 43 (37%) as SCLC like. The median overall survival (OS) from the start of first-line therapy was 10.0 months (95% confidence interval: 8.6-11.9) for patients with primary LCNEC and 16.3 months (9.4-40) for tLCNEC. There was no statistical difference in OS between patients treated with NSCLC or SCLC regimens (median OS: 12.1 mo [10.0-17.6] versus 9.4 mo [6.3-11.2]) or with the addition of immunotherapy to chemotherapy (median OS: 9.9 mo [7.7-13.9] versus 10.4 mo [8.6-14.1]). Several patients with tLCNEC who received local therapies for oligometastatic disease had long-term disease control.

Clinical outcomes for patients with LCNEC are poor, with no clear association of benefit observed through the application of molecularly classified standard treatments. Based on these data, we propose guidelines for the development of prospective trials of novel therapeutics aimed at addressing the unmet needs of this patient population.