Brigatinib Continues to Best Crizotinib in ALK+ Non-Small Cell Lung Cancer

Masked doctor and patient talking to each other.
Masked doctor and patient talking to each other.
There was an improvement in progression-free survival despite crossover.

The following article features coverage from the European Society of Medical Oncology (ESMO) Congress 2021. Click here to read more of MPR‘s conference coverage.

Final results from a phase 3 trial showed that brigatinib continued to improve progression-free survival (PFS) compared with crizotinib in patients with advanced, ALK-positive non-small cell lung cancer (NSCLC).1

These results, from the ALTA1-L study ( Identifier: NCT02737501), were presented in a poster at the European Society for Medical Oncology (ESMO) Congress 2021.

The study enrolled adults with stage IIIB/IV, ALK-positive NSCLC who had not received a prior ALK inhibitor but had received at least 1 prior systemic treatment for locally advanced or metastatic NSCLC. A total of 275 patients were randomly assigned to receive brigatinib (137 patients) or crizotinib (138 patients).

Two prior analyses showed improved PFS with brigatinib.2,3 For the current analysis, the median follow-up was 40.4 months in patients who received brigatinib and 15.2 months for crizotinib.

In all, 42% of patients in the brigatinib arm and 12% of those in the crizotinib arm were still on study treatment before the end of the study. Nearly half of patients in the crizotinib arm (47%) crossed over to the brigatinib arm after disease progression.

Patients in the crizotinib arm were more likely than those in the brigatinib arm to receive subsequent systemic therapy (85% and 59%, respectively), another ALK inhibitor (82% vs 54%), radiotherapy (12% vs 3%), and surgery (2% vs 0%), but not chemotherapy or other targeted therapy (17% vs 21%).  


According to a blinded independent review committee (BIRC), the median PFS was 24.0 months in the brigatinib arm and 11.1 months in the crizotinib arm (hazard ratio [HR], 0.48; 95% CI, 0.35-0.66; P <.0001). The 4-year PFS rates were 36% and 18%, respectively.

The median intracranial PFS, per BIRC assessment, was 24.0 months in the brigatinib arm and 5.5 months in the crizotinib arm (HR, 0.29; 95% CI, 0.17-0.51; P <.0001). The 4-year intracranial PFS rates were 22% and not estimable, respectively.

Overall survival (OS) data were not mature at the time of the analysis, but the results appeared to be similar between the treatment arms. However, the researchers conducted a sensitivity analysis to adjust for possible confounding from crossover, and the results suggested that brigatinib would have been associated with improved OS if crossover had not been permitted.

The 4-year OS rate was 66% in the brigatinib arm and 60% in the crizotinib arm. In the overall OS analysis, the HR was 0.81 (95% CI, 0.53-1.22; P =.305). In the sensitivity analysis adjusting for crossover, the HR was 0.54 (95% CI, 0.31-0.92; P =.023).

The researchers also noted an improvement in OS with brigatinib among patients with brain metastases at baseline. In this group, the 4-year OS rate was 71% in the brigatinib arm and 44% in the crizotinib arm (HR, 0.43; 95% CI, 0.21-0.89; P =.020).

The safety data were consistent with the data in the 2 prior analyses, and no new safety signals were identified, according to the researchers.

“These results support brigatinib as a standard treatment option for treatment-naive ALK+ NSCLC,” the researchers concluded.

Disclosures: This research was supported by ARIAD Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Popat S, Kim, HR, Ahn MJ, et al. Brigatinib (BRG) vs crizotinib (CRZ) in ALK TKI–naive ALK+ NSCLC: Final results from ALTA-1L. Presented at: European Society of Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 1195P.
  2. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379(21):2027-2039. doi:10.1056/NEJMoa1810171
  3. Camidge DR, Kim HR, Ahn MJ, et al. 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. J Clin Oncol. 2020;38(31):3592-3603. doi:10.1200/JCO.20.00505

This article originally appeared on Cancer Therapy Advisor