Makoto Nishio1, Tatsuya Yoshida2, Toru Kumagai3, Toyoaki Hida4, Ryo Toyozawa5, Tadasuke Shimokawaji6, Koichi Goto7, Kazuhiko Nakagawa8, Yuichiro Ohe2, Takashi Seto5, Kentarou Kudou9, Takayuki Asato10, Pingkuan Zhang11, Nobuyuki Yamamoto12. 1. Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo, Japan. 2. Department of Thoracic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. 3. Department of Thoracic Oncology, Osaka International Cancer Institute, Chuo-ku, Osaka, Japan. 4. Department of Thoracic Oncology, Aichi Cancer Center, Nagoya, Aichi, Japan. 5. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka, Japan. 6. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. 7. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan. 8. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan. 9. Biostatistics, Japan Development Center, Takeda Pharmaceutical Company Limited, Chuo-ku, Osaka, Japan. 10. Oncology Clinical Research Department, Oncology Therapeutic Area Unit for Japan and Asia, Takeda Pharmaceutical Company Limited, Chuo-ku, Osaka, Japan. 11. Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts. 12. Internal Medicine III, Wakayama Medical University, Wakayama, Wakayama Prefecture, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp.
Abstract
INTRODUCTION: This phase 2 trial evaluated the efficacy and safety of brigatinib in patients with advanced ALK-positive NSCLC refractory to alectinib or other ALK tyrosine kinase inhibitors (TKIs). METHODS: This single-arm, multicenter, open-label study in Japanese patients consisted of a safety lead-in followed by an expansion stage in patients refractory to ALK TKI or those naive for ALK TKI. Patients received brigatinib 180 mg once daily with 7-day lead-in at 90 mg once daily. Primary end point was independent review committee (IRC)-assessed confirmed objective response rate per the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: We report the results of the lead-in and expansion in the patients refractory to ALK TKI. Of 72 patients enrolled, 47 had alectinib as most recent ALK TKI (with or without previous crizotinib). At analysis cutoff, 14 of the 47 remained on brigatinib (median follow-up: 12.4 mo). In the alectinib-refractory population, IRC-assessed confirmed objective response rate was 34% (95% confidence interval [CI]: 21%-49%) with median duration of response of 11.8 months (95% CI: 5.5-16.4). Disease control rate was 79% (95% CI: 64%-89%). Median IRC-assessed progression-free survival was 7.3 months (95% CI: 3.7-9.3). Two of eight patients with measurable brain lesions at baseline had confirmed intracranial partial response. Brigatinib has been found to have antitumor activity in patients with G1202R, I1171N, V1180L, and L1196M secondary mutations. The safety profile in Japanese patients was consistent with that in previous reports in broader populations. CONCLUSIONS: Brigatinib has been found to have clinically meaningful efficacy in Japanese patients with ALK+ NSCLC refractory to alectinib (with or without previous crizotinib).
INTRODUCTION: This phase 2 trial evaluated the efficacy and safety of brigatinib in patients with advanced ALK-positive NSCLC refractory to alectinib or other ALK tyrosine kinase inhibitors (TKIs). METHODS: This single-arm, multicenter, open-label study in Japanese patients consisted of a safety lead-in followed by an expansion stage in patients refractory to ALK TKI or those naive for ALK TKI. Patients received brigatinib 180 mg once daily with 7-day lead-in at 90 mg once daily. Primary end point was independent review committee (IRC)-assessed confirmed objective response rate per the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: We report the results of the lead-in and expansion in the patients refractory to ALK TKI. Of 72 patients enrolled, 47 had alectinib as most recent ALK TKI (with or without previous crizotinib). At analysis cutoff, 14 of the 47 remained on brigatinib (median follow-up: 12.4 mo). In the alectinib-refractory population, IRC-assessed confirmed objective response rate was 34% (95% confidence interval [CI]: 21%-49%) with median duration of response of 11.8 months (95% CI: 5.5-16.4). Disease control rate was 79% (95% CI: 64%-89%). Median IRC-assessed progression-free survival was 7.3 months (95% CI: 3.7-9.3). Two of eight patients with measurable brain lesions at baseline had confirmed intracranial partial response. Brigatinib has been found to have antitumor activity in patients with G1202R, I1171N, V1180L, and L1196M secondary mutations. The safety profile in Japanese patients was consistent with that in previous reports in broader populations. CONCLUSIONS:Brigatinib has been found to have clinically meaningful efficacy in Japanese patients with ALK+ NSCLC refractory to alectinib (with or without previous crizotinib).
Authors: Flávia Melo Cunha de Pinho Pessoa; Caio Bezerra Machado; Emerson Lucena da Silva; Laudreísa da Costa Pantoja; Rodrigo Monteiro Ribeiro; Maria Elisabete Amaral de Moraes; Manoel Odorico de Moraes Filho; Raquel Carvalho Montenegro; André Salim Khayat; Caroline Aquino Moreira-Nunes Journal: Int J Mol Sci Date: 2022-03-30 Impact factor: 5.923
Authors: Randa Mohammed Zaki; Munerah M Alfadhel; Saad M Alshahrani; Ahmed Alsaqr; Layla A Al-Kharashi; Md Khalid Anwer Journal: Pharmaceuticals (Basel) Date: 2022-03-13