Waliany Sarah, Hung Yin P, Rous Fawzi Abu, Luo Faustine, Capelletti Marzia, Ressler Steven, Do Andrew, Peterson Jennifer, Meservey Caitlin, Digumarthy Subba R, Ou Sai-Hong Ignatius, Gadgeel Shirish M, Lin Jessica J, Meador Catherine B
Massachusetts General Hospital Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, MA.
Department of Pathology, Massachusetts General Hospital, Boston, MA.
Clin Lung Cancer. 2025 Jul;26(5):354-363.e5. doi: 10.1016/j.cllc.2025.03.009. Epub 2025 Mar 25.
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.
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.
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%.
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.
晚期肺类癌患者的有效治疗方法仍然有限。肺类癌中潜在可操作的基因组改变（AGA）的患病率尚不清楚。
回顾性研究2013年9月至2024年3月在一家临床实验室改进修正案（CLIA）认证的基因组学实验室提交进行下一代测序（NGS）的肺类癌，以确定AGA的患病率。我们评估了在3家机构中识别出AGA的晚期肺类癌患者接受基因型匹配的靶向治疗的结果，并进行了全面的文献检索。
在通过NGS分析的321例肺类癌病例中，8例（2.5%）存在潜在的AGA（4例[1.2%]有可商购的靶向治疗药物），包括KRAS突变（n = 4，1.2%：G12C、G12D、G12R、G12V）、ALK融合（n = 2，0.6%）、BRAF D594N（n = 1，0.3%）和RET融合（n = 1，0.3%）。24例典型类癌均未携带AGA。综合这些数据库识别的患者、我们的多机构队列和文献综述，我们确定了36例有潜在AGA的肺类癌（24例有可商购的靶向治疗药物），主要包括ALK（n = 14）、RET（n = 5）和NTRK（n = 2）的融合。在27例已知疾病分期的患者中，19例为4期疾病，13例（68.4%）报告了靶向治疗后的结果。中位治疗持续时间为12.0个月（95%CI：6.7 - 16.0）。所有靶向治疗线的中位无进展生存期（PFS）为10.6个月（95%CI：6.7 - 16.0），一线靶向治疗为14.0个月（95%CI：1.3 - NA）。至少接受一种靶向治疗的客观缓解率为61.5%。
携带AGA的晚期肺类癌患者可从基因型匹配的靶向治疗中获得有意义的益处，突出了NGS在晚期类癌患者中的潜在作用。
