Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-03-04 DOI:10.1016/j.ejca.2025.115338

Changsong Qi , Lin Shen , Thierry Andre , Hyun Cheol Chung , Timothy L. Cannon , Elena Garralda , Antoine Italiano , Damian T. Rieke , Tianshu Liu , Domnita-Ileana Burcoveanu , Natascha Neu , Chiara E. Mussi , Rui-Hua Xu , David S. Hong , Alexander Drilon , Jordan Berlin

{"title":"Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer","authors":"Changsong Qi , Lin Shen , Thierry Andre , Hyun Cheol Chung , Timothy L. Cannon , Elena Garralda , Antoine Italiano , Damian T. Rieke , Tianshu Liu , Domnita-Ileana Burcoveanu , Natascha Neu , Chiara E. Mussi , Rui-Hua Xu , David S. Hong , Alexander Drilon , Jordan Berlin","doi":"10.1016/j.ejca.2025.115338","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.</div></div><div><h3>Methods</h3><div>Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.</div></div><div><h3>Results</h3><div>As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients with CRC, 16 (62 %) had known microsatellite instability-high (MSI-H) status. For the 43 IRC-eligible patients, overall response rate was 28 % (95 % confidence interval [CI] 15–44) for all patients and 44 % (95 % CI 24–65) for those with CRC. In patients overall and in those with CRC, median duration of response was 27 months (95 % CI 6–not estimable [NE]) and 27 months (95 % CI 6–NE), median progression-free survival was 6 months (95 % CI 5–9) and 7 months (95 % CI 6–NE), and median overall survival was 13 months (95 % CI 7–29) and 29 months (95 % CI 7–NE), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in seven (16 %) patients. There were no deaths due to TRAEs.</div></div><div><h3>Conclusion</h3><div>Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC. This supports the wider adoption of next-generation sequencing testing for <em>NTRK</em> gene fusions in patients with GI cancer.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115338"},"PeriodicalIF":7.6000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804925001194","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods

Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results

As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients with CRC, 16 (62 %) had known microsatellite instability-high (MSI-H) status. For the 43 IRC-eligible patients, overall response rate was 28 % (95 % confidence interval [CI] 15–44) for all patients and 44 % (95 % CI 24–65) for those with CRC. In patients overall and in those with CRC, median duration of response was 27 months (95 % CI 6–not estimable [NE]) and 27 months (95 % CI 6–NE), median progression-free survival was 6 months (95 % CI 5–9) and 7 months (95 % CI 6–NE), and median overall survival was 13 months (95 % CI 7–29) and 29 months (95 % CI 7–NE), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in seven (16 %) patients. There were no deaths due to TRAEs.

Conclusion

Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC. This supports the wider adoption of next-generation sequencing testing for NTRK gene fusions in patients with GI cancer.

查看原文本刊更多论文

larorectinib治疗TRK融合胃肠道肿瘤的疗效和安全性

larorectinib是一流的高选择性TRK抑制剂，在各种TRK融合实体瘤中显示出疗效。我们报道了larorectinib在TRK融合胃肠道（GI）癌患者中的有效性和安全性。方法纳入来自NAVIGATE （NCT02576431）的TRK融合GI癌患者。响应由独立审查委员会（IRC）根据RECIST v1.1进行评估。结果截至2023年7月，44例患者入组。肿瘤类型包括结直肠（CRC）；N = 26)，胰腺癌（N = 7），胆管癌（N = 4），胃癌（N = 3），阑尾癌，十二指肠癌，食管癌和肝癌各1例。在26例结直肠癌患者中，16例（62% %）已知微卫星不稳定性高（MSI-H）状态。对于43名符合irc条件的患者，所有患者的总缓解率为28 %(95% %可信区间[CI] 15-44)， CRC患者的总缓解率为44 %（95% % CI 24-65）。在总体患者和结直肠癌患者中，中位缓解持续时间为27个月（95 % CI 6 -不可估计[NE]）和27个月（95 % CI 6 - NE），中位无进展生存期为6个月（95 % CI 5-9）和7个月（95 % CI 6 - NE），中位总生存期分别为13个月（95 % CI 7 - 29）和29个月（95 % CI 7 - NE）。7例（16% %）患者发生3/4级治疗相关不良事件（TRAEs）。没有人死于trae。结论larorectinib在TRK融合的GI癌患者（包括MSI-H型结直肠癌患者）中表现出持久、延长的生存期和可管理的安全性。这支持在胃肠道癌患者中更广泛地采用下一代NTRK基因融合测序检测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.