Dataset Information

Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials.

ABSTRACT:

Introduction

We report brigatinib long-term efficacy and safety from phase 1/2 and phase 2 (ALTA) trials in ALK-rearrangement positive (ALK+) NSCLC.

Methods

The phase 1/2 study evaluated brigatinib 30 to 300 mg/d in patients with advanced malignancies. ALTA randomized patients with crizotinib-refractory ALK+ NSCLC to brigatinib 90 mg once daily (arm A) or 180 mg once daily (7-d lead-in at 90 mg; arm B).

Results

In the phase 1/2 study, 79 of 137 brigatinib-treated patients had ALK+ NSCLC; 71 were crizotinib pretreated. ALTA randomized 222 patients (n = 112 in arm A; n = 110 in arm B). Median follow-up at phase 1/2 study end (≈5.6 y after last patient enrolled) was 27.7 months; at ALTA study end (≈4.4 y after last patient enrolled), 19.6 months (A) and 28.3 months (B). Among patients with ALK+ NSCLC in the phase 1/2 study, median investigator-assessed progression-free survival (PFS) was 14.5 months (95% confidence interval [CI]: 10.8-21.2); median overall survival was 47.6 months (28.6-not reached). In ALTA, median investigator-assessed PFS was 9.2 months (7.4-11.1) in arm A and 15.6 months (11.1-18.5) in arm B; median independent review committee (IRC)-assessed PFS was 9.9 (7.4-12.8) and 16.7 (11.6-21.4) months, respectively; median overall survival was 25.9 (18.2-45.8) and 40.6 (32.5-not reached) months, respectively. Median intracranial PFS for patients with any brain metastases was 12.8 (9.2-18.4) months in arm A and 18.4 (12.6-23.9) months in arm B. No new safety signals were identified versus previous analyses.

Conclusions

Brigatinib exhibited sustained long-term activity and PFS with manageable safety in patients with crizotinib-refractory ALK+ NSCLC.

SUBMITTER: Gettinger SN

PROVIDER: S-EPMC9440305 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory <i>ALK</i>+ NSCLC: Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials.

Gettinger Scott N SN Huber Rudolf M RM Kim Dong-Wan DW Bazhenova Lyudmila L Hansen Karin Holmskov KH Tiseo Marcello M Langer Corey J CJ Paz-Ares Rodríguez Luis G LG West Howard L HL Reckamp Karen L KL Weiss Glen J GJ Smit Egbert F EF Hochmair Maximilian J MJ Kim Sang-We SW Ahn Myung-Ju MJ Kim Edward S ES Groen Harry J M HJM Pye Joanna J Liu Yuyin Y Zhang Pingkuan P Vranceanu Florin F Camidge D Ross DR

JTO clinical and research reports 20220731 9

<h4>Introduction</h4>We report brigatinib long-term efficacy and safety from phase 1/2 and phase 2 (ALTA) trials in <i>ALK</i>-rearrangement positive (<i>ALK</i>+) NSCLC.<h4>Methods</h4>The phase 1/2 study evaluated brigatinib 30 to 300 mg/d in patients with advanced malignancies. ALTA randomized patients with crizotinib-refractory <i>ALK+</i> NSCLC to brigatinib 90 mg once daily (arm A) or 180 mg once daily (7-d lead-in at 90 mg; arm B).<h4>Results</h4>In the phase 1/2 study, 79 of 137 brigatin ...[more]

PMID: 36065449

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