Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: a case series from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-04-10 DOI:10.1016/j.esmoop.2025.104545

J. Rodon , M. Rothe , P.K. Mangat , E. Garrett-Mayer , T.L. Cannon , E. Hobbs , G.P. Kalemkerian , D.C. Hinshaw , A. Gregory , G.N. Grantham , S. Halabi , R.L. Schilsky

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Abstract

Background

TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Results of four patients with various tumors with NRG1 fusions treated with afatinib are reported.

Patients and methods

Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with NRG1 fusions, and no standard treatment options. The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks’ duration (SD16+). Secondary endpoints included OR, duration of response, duration of SD, and safety.

Results

Four patients were enrolled from February 2020 to July 2021; all had solid tumors [colorectal cancer (n = 2), non-small-cell lung cancer (n = 1), and pancreatic adenocarcinoma (n = 1)] with an NRG1 fusion. All patients were evaluable for efficacy. One partial response and two SD16+ were observed. One patient was still alive as of October 2024 with SD of 134 weeks’ duration. No patients had a drug-related grade 3-5 adverse event (AE) or serious AE.

Conclusion

Though the sample size was small, afatinib demonstrated promising activity in patients with advanced solid tumors with NRG1 fusions, including durable DC warranting additional study.

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阿法替尼治疗伴有神经调节蛋白1 （NRG1）融合的实体肿瘤患者：来自靶向药物和分析使用登记（TAPUR）研究的病例系列

tapur是一项II期篮子试验，评估市售靶向药物对晚期癌症和可靶向基因组改变患者的抗肿瘤活性。本文报道了4例不同类型NRG1融合肿瘤患者用阿法替尼治疗的结果。患者和方法入选的患者为晚期癌症、可测量疾病（RECIST）、东部肿瘤合作组织（Eastern Cooperative Oncology Group）评分0-2、器官功能充足、肿瘤存在NRG1融合、无标准治疗方案。主要终点是疾病控制（DC），定义为客观缓解（OR）或至少16周持续时间（SD16+）的疾病稳定（SD）。次要终点包括OR、反应持续时间、SD持续时间和安全性。结果4例患者于2020年2月至2021年7月入组；所有患者均有NRG1融合的实体瘤[结直肠癌（n = 2）、非小细胞肺癌（n = 1）和胰腺腺癌（n = 1）]。所有患者均可评估疗效。观察到1例部分缓解和2例SD16+。截至2024年10月，1名患者仍然存活，SD持续时间为134周。没有患者发生与药物相关的3-5级不良事件（AE）或严重AE。尽管样本量很小，但阿法替尼在NRG1融合的晚期实体瘤患者中显示出有希望的活性，包括需要进一步研究的持久DC。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.