Compassionate Access to Brigatinib for Patients with Non-small-cell Lung Cancer Harboring a ROS1 Rearrangement: Results from the BRIGAROS Study

Target Oncol. 2025 Mar;20(2):311-317. doi: 10.1007/s11523-025-01131-x. Epub 2025 Mar 13.

Abstract

Background: ROS1 chromosomic rearrangement is a rare oncogenic driver, and patients with this rearrangement benefit from specific targeted treatments in the first-line setting. However, therapeutic options are limited in pretreated patients. Brigatinib is a validated drug for ALK rearrangements, and also has an in vitro activity against ROS1. In vivo efficacy is also suggested in some clinical series.

Objective: We aimed to specifically study brigatinib in patients with pretreated advanced non-small-cell lung cancer (NSCLC).

Methods: We retrospectively collected data from 20 centers in France. Brigatinib was delivered through a compassionate use program in France between 2018 and 2020. The primary endpoint was progression-free survival. Secondary endpoints were the objective response rate, overall survival, and tolerance.

Results: Twenty-five patients treated with brigatinib were included in our study. All patients were pretreated, and all of them previously received crizotinib. Median progression-free survival was 3.8 months (95% confidence interval 2.8-7.1). The objective response rate was 32%, with a disease control rate of 48%. Three patients had a prolonged response of more than 18 months at the end of data collection. We did not identify factors predictive of prolonged response. There were no grade 4 or 5 toxicities.

Conclusion: Brigatinib may represent an interesting therapeutic option for patients who have progressed after standard treatments.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Compassionate Use Trials
  • Female
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Organophosphorus Compounds* / pharmacology
  • Organophosphorus Compounds* / therapeutic use
  • Protein-Tyrosine Kinases* / genetics
  • Proto-Oncogene Proteins* / genetics
  • Pyrimidines* / pharmacology
  • Pyrimidines* / therapeutic use
  • Retrospective Studies

Substances

  • ROS1 protein, human
  • brigatinib
  • Organophosphorus Compounds
  • Pyrimidines
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases