Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial.

Abstract

PURPOSE:

Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501). We report results of the second prespecified interim analysis (150 events).

METHODS:

Patients with ALK inhibitor-naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected.

RESULTS:

Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration-time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69).

CONCLUSION:

Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.

• 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 García Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander Spira, Scott N Gettinger, Marcello Tiseo, Huamao M Lin, Neeraj Gupta, Michael J Hanley, Quanhong Ni, Pingkuan Zhang, Sanjay Popat
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 31 Pg. 3592-3603 (11 01 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 32780660 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organophosphorus Compounds
• Pyrimidines
• Crizotinib
• Anaplastic Lymphoma Kinase
• brigatinib

Topics

• Adolescent
• Adult
• Aged
• Anaplastic Lymphoma Kinase (antagonists & inhibitors, metabolism)
• Antineoplastic Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Crizotinib (adverse effects, blood, pharmacokinetics, therapeutic use)
• Female
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• Male
• Middle Aged
• Organophosphorus Compounds (adverse effects, blood, pharmacokinetics, therapeutic use)
• Progression-Free Survival
• Pyrimidines (adverse effects, blood, pharmacokinetics, therapeutic use)
• Quality of Life
• Survival Rate
• Young Adult