Lung Carcinoid Tumors With Potentially Actionable Genomic Alterations and Responses to Targeted Therapies

Document Type

Article

Publication Date

7-1-2025

Publication Title

Clinical lung cancer

Abstract

BACKGROUND: Effective treatments for patients with advanced lung carcinoids remain limited. The prevalence of potentially actionable genomic alterations (AGAs) among lung carcinoids is not well-understood.

MATERIALS AND METHODS: Lung carcinoids submitted for next-generation sequencing (NGS) at a Clinical Laboratory Improvement Amendments (CLIA)-certified genomics laboratory from September 2013 to March 2024 were retrospectively investigated to determine prevalence of AGAs. We evaluated outcomes with genotype-matched targeted therapies in patients with advanced lung carcinoids with AGAs identified across 3 institutions and comprehensive literature search.

RESULTS: Among 321 cases of lung carcinoids profiled by NGS, 8 (2.5%) harbored potential AGAs (4 [1.2%] with commercially available targeted therapies), including KRAS mutations (n = 4, 1.2%: G12C, G12D, G12R, G12V), ALK fusions (n = 2, 0.6%), BRAF D594N (n = 1, 0.3%), and RET fusion (n = 1, 0.3%). None of the 24 typical carcinoids harbored an AGA. Collectively across these database-identified patients, our multi-institutional cohort, and literature review, we identified 36 cases of lung carcinoids with potential AGAs (24 with commercially available targeted therapies), predominantly comprising fusions of ALK (n = 14), RET (n = 5), and NTRK (n = 2). Of 27 with known disease stage, 19 had stage 4 disease, and 13 (68.4%) had outcomes reported following targeted therapies. Median treatment duration was 12.0 months (95% CI: 6.7-16.0). Median progression-free survival (PFS) was 10.6 months (95% CI: 6.7-16.0) across all targeted therapy lines and 14.0 months (95% CI: 1.3-NA) with first-line targeted therapies. Objective response rate with at least one targeted therapy was 61.5%.

CONCLUSIONS: Patients with advanced lung carcinoids harboring AGAs can derive meaningful benefit from genotype-matched targeted therapies, highlighting potential role for NGS in patients with advanced carcinoids.

Medical Subject Headings

Humans; Lung Neoplasms; Carcinoid Tumor; Male; Middle Aged; Female; Molecular Targeted Therapy; Retrospective Studies; Aged; Mutation; Adult; High-Throughput Nucleotide Sequencing; Genomics; Biomarkers, Tumor; Prognosis; Aged, 80 and over; Follow-Up Studies

PubMed ID

40234130

Volume

26

Issue

5

First Page

354

Last Page

363

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