Sarah Waliany, Yin P Hung, Fawzi Abu Rous, Faustine Luo, Marzia Capelletti, Steven Ressler, Andrew Do, Jennifer Peterson, Caitlin Meservey, Subba R Digumarthy, Sai-Hong Ignatius Ou, Shirish M Gadgeel, Jessica J Lin, Catherine B Meador
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引用次数: 0
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.
期刊介绍：
Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.
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