Thomas E Stinchcombe1, Robert C Doebele2, Xiaofei Wang3, David E Gerber4, Leora Horn5, D Ross Camidge2. 1. Division of Medical Oncology, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina. Electronic address: Thomas.stinchcombe@duke.edu. 2. Division of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado. 3. Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina. 4. Division of Hematology-Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas. 5. Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
Abstract
INTRODUCTION: Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor (TKI) with activity against ALK resistance mutations and central nervous system activity. We prospectively studied the activity and safety of brigatinib in patients with disease progression after other next-generation ALK TKIs. METHODS: Patients with stage IIIB or IV ALK+ NSCLC and progressive disease after next-generation ALK TKIs were eligible. Patients were required to undergo tumor biopsy less than or equal to 60 days before enrollment, and circulating tumor DNA was collected at baseline. Brigatinib treatment was 90 mg daily for 7 days and then escalated to 180 mg daily. Primary end point was objective response rate, and two-stage design was used. RESULTS: Between March 2017 and November 2018, a total of 20 patients were treated in stage 1; median age was 55 years (range: 32-71), median number of previous therapies was three (range: 1-6), median number of previous ALK TKIs was two (range: 1-4), and 11 had central nervous system disease at baseline. The objective response rate was 40% (95% confidence interval [CI]: 19%-62%), and the duration of response was 5.3 months (95% CI: 3.6-nonassessable). With follow-up of 22 months, the median progression-free survival was 7.0 months (95% CI: 4.6-10.1). Grade 3 or 4 adverse events were consistent with those of previous studies. CONCLUSIONS: Brigatinib has activity in ALK+ NSCLC after previous next-generation ALK TKIs. Further study in patients with disease progression on next-generation ALK TKI is warranted. National Clinical Trials #: NCT02706626.
INTRODUCTION:Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor (TKI) with activity against ALK resistance mutations and central nervous system activity. We prospectively studied the activity and safety of brigatinib in patients with disease progression after other next-generation ALK TKIs. METHODS:Patients with stage IIIB or IV ALK+ NSCLC and progressive disease after next-generation ALK TKIs were eligible. Patients were required to undergo tumor biopsy less than or equal to 60 days before enrollment, and circulating tumor DNA was collected at baseline. Brigatinib treatment was 90 mg daily for 7 days and then escalated to 180 mg daily. Primary end point was objective response rate, and two-stage design was used. RESULTS: Between March 2017 and November 2018, a total of 20 patients were treated in stage 1; median age was 55 years (range: 32-71), median number of previous therapies was three (range: 1-6), median number of previous ALK TKIs was two (range: 1-4), and 11 had central nervous system disease at baseline. The objective response rate was 40% (95% confidence interval [CI]: 19%-62%), and the duration of response was 5.3 months (95% CI: 3.6-nonassessable). With follow-up of 22 months, the median progression-free survival was 7.0 months (95% CI: 4.6-10.1). Grade 3 or 4 adverse events were consistent with those of previous studies. CONCLUSIONS:Brigatinib has activity in ALK+ NSCLC after previous next-generation ALK TKIs. Further study in patients with disease progression on next-generation ALK TKI is warranted. National Clinical Trials #: NCT02706626.
Authors: Zhengfei Zhu; Jianjiao Ni; Xuwei Cai; Shengfa Su; Hongqing Zhuang; Zhenzhou Yang; Ming Chen; Shenglin Ma; Conghua Xie; Yaping Xu; Jiancheng Li; Hong Ge; Anwen Liu; Lujun Zhao; Chuangzhou Rao; Congying Xie; Nan Bi; Zhouguang Hui; Guangying Zhu; Zhiyong Yuan; Jun Wang; Lina Zhao; Wei Zhou; Chai Hong Rim; Arturo Navarro-Martin; Ben G L Vanneste; Dirk De Ruysscher; J Isabelle Choi; Jacek Jassem; Joe Y Chang; Lucyna Kepka; Lukas Käsmann; Michael T Milano; Paul Van Houtte; Rafal Suwinski; Alberto Traverso; Hiroshi Doi; Yang-Gun Suh; Georges Noël; Natsuo Tomita; Roman O Kowalchuk; Terence T Sio; Baosheng Li; Bing Lu; Xiaolong Fu Journal: Transl Lung Cancer Res Date: 2022-09