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Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial

Authors
 D Ross Camidge  ;  Hye Ryun Kim  ;  Myung-Ju Ahn  ;  James C H Yang  ;  Ji-Youn Han  ;  Maximilian J Hochmair  ;  Ki Hyeong Lee  ;  Angelo Delmonte  ;  Maria Rosario Garcia Campelo  ;  Dong-Wan Kim  ;  Frank Griesinger  ;  Enriqueta Felip  ;  Raffaele Califano  ;  Alexander I Spira  ;  Scott N Gettinger  ;  Marcello Tiseo  ;  Huamao M Lin  ;  Yuyin Liu  ;  Florin Vranceanu  ;  Huifeng Niu  ;  Pingkuan Zhang  ;  Sanjay Popat 
Citation
 JOURNAL OF THORACIC ONCOLOGY, Vol.16(12) : 2091-2108, 2021-12 
Journal Title
JOURNAL OF THORACIC ONCOLOGY
ISSN
 1556-0864 
Issue Date
2021-12
MeSH
Anaplastic Lymphoma Kinase / genetics ; Crizotinib / therapeutic use ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Organophosphorus Compounds ; Protein Kinase Inhibitors / therapeutic use ; Pyrimidines / therapeutic use
Keywords
ALK tyrosine kinase inhibitor ; Anaplastic lymphoma kinase ; Brigatinib ; Crizotinib ; Non–small cell lung cancer
Abstract
Introduction: In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results.

Methods: Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy.

Results: A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35-0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53-1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed.

Conclusions: In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.
Files in This Item:
T202126214.pdf Download
DOI
10.1016/j.jtho.2021.07.035
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190628
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