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. 2025 May:203:108478.
doi: 10.1016/j.lungcan.2025.108478. Epub 2025 Mar 12.

Real-world safety and effectiveness of entrectinib in Japanese patients with ROS1 gene fusion-positive, unresectable, advanced/recurrent non-small cell lung cancer: Post-marketing surveillance

Takashi Seto  1 , Sayuri Nakane  2 , Lyu Ji  2 , Yuya Ueda  2 , Hiroshi Sugano  2 , Nobuki Takei  2 , Mizuki Kobayashi  2 , Ayako Murayama  2 , Noboru Yamamoto  3
Affiliations
Free article

Real-world safety and effectiveness of entrectinib in Japanese patients with ROS1 gene fusion-positive, unresectable, advanced/recurrent non-small cell lung cancer: Post-marketing surveillance

Takashi Seto et al. Lung Cancer. 2025 May.
Free article

Abstract

Objectives: To evaluate the safety and effectiveness of entrectinib, an orally-administered potent multi-kinase inhibitor, for the treatment of proto-oncogene tyrosine-protein kinase-1 (ROS1) gene fusion-positive, unresectable, advanced/recurrent non-small cell lung cancer (NSCLC) in Japan.

Materials and methods: Patients with ROS1 gene fusion-positive, unresectable, advanced/recurrent NSCLC who initiated entrectinib therapy were enrolled in this all-case post marketing surveillance between February 21, 2020 and November 30, 2021. Outcomes were to identify the: (1) type and onset of initial cognitive disorder and ataxia during entrectinib therapy; (2) status of treatment and outcome of drug-related cognitive disorder and ataxia events; (3) incidence of other adverse drug reactions (ADRs) of safety concern: cognitive disorder and/or ataxia, cardiac disorder (excluding QT interval prolongation), QT interval prolongation, syncope, and interstitial lung disease; (4) incidence of serious adverse events (AEs) and ADRs; and (5) effectiveness.

Results: Of the 276 patients who initiated entrectinib, 269 and 260 were included in the safety and effectiveness analysis sets, respectively. Cognitive disorder/ataxia was the most common ADR of safety concern, occurring in 72 patients (26.8 %). The median time to onset of initial cognitive disorder/ataxia symptoms was 2.0 days. Overall, entrectinib dose reduction, interruption, or discontinuation occurred in 9.7 %, 28.3 %, and 15.2 % of patients, respectively. Most ADRs of safety concern were manageable; 86.9 % of patients with ADRs were recovered/recovering. Serious AEs were reported in 42.8 % of patients. The overall response rate (ORR) was 38.8 % and median time to treatment failure was 6.4 months. ORR was 70.8 % versus 26.8 % to 34.7 % with entrectinib as first-line versus second- or later-line treatment, and 65.3 % versus 28.2 % in patients without versus with a history of tyrosine kinase inhibitor treatment.

Conclusions: Consistent with clinical trials, entrectinib is tolerable and effective in Japanese patients with ROS1 gene fusion-positive, unresectable, advanced/recurrent NSCLC.

Study registration: UMIN Clinical Trials Registry (UMIN000046619).

Keywords: Entrectinib; Japan; Non-small-cell lung cancer; Post-marketing surveillance; ROS1 fusion gene; ROS1 tyrosine kinase inhibitors.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takashi Seto has received honoraria for lectures from Amgen, AnHeart Therapeutics, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, GlaxoSmithKline, MSD, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Takeda Pharmaceutical, and Towa Pharmaceutical; and is an employee of Precision Medicine Asia. Noboru Yamamoto has received grants/contracts from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Carna Biosciences, Chiome Bioscience, Chugai Pharmaceutical, CMIC Group, Daiichi-Sankyo, Eisai, Eli Lilly, Genmab, GlaxoSmithKline, InventisBio, Janssen Pharma, Kaken Pharmaceutical Co. Ltd., Kyowa Kirin, Merck, MSD, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer Japan, Rakuten Medical, Shionogi, Sumitomo Pharma, Taiho, Takeda, and Toray Industries Inc. Sayuri Nakane, Lyu Ji, Yuya Ueda, Hiroshi Sugano, Nobuki Takei, Mizuki Kobayashi, and Ayako Murayama are employees of Chugai Pharmaceutical.

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