Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial

Rudolf M Huber*, Karin H Hansen, Luis Paz-Ares Rodríguez, Howard L West, Karen L Reckamp, Natasha B Leighl, Marcello Tiseo, Egbert F Smit, Dong-Wan Kim, Scott N Gettinger, Maximilian J Hochmair, Sang-We Kim, Corey J Langer, Myung-Ju Ahn, Edward S Kim, David Kerstein, Harry J M Groen, D Ross Camidge

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

89 Citaten (Scopus)
69 Downloads (Pure)

Samenvatting

Introduction: We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase–positive NSCLC. Methods: Patients were randomized 1:1 to take either oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS. Results: Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4–12.8) versus 16.7 months (11.6–21.4). Median OS was 29.5 months (18.2–not reached) versus 34.1 months (27.7–not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%–25%, 26%–50%, 51%–75%, and 76%–100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up. Conclusions: Brigatinib (180 mg once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials.

Originele taal-2English
Pagina's (van-tot)404-415
Aantal pagina's12
TijdschriftJournal of Thoracic Oncology
Volume15
Nummer van het tijdschrift3
Vroegere onlinedatum19-nov.-2019
DOI's
StatusPublished - mrt.-2020

Citeer dit