Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Mar;20(2):311-317.
doi: 10.1007/s11523-025-01131-x. Epub 2025 Mar 13.

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

Jean Mourlanette  1 , Gaelle Rousseau-Bussac  2 , Siham Mallah  1 , Florian Guisier  3 , Gerard Zalcman  4 , Rémi Veillon  5 , Clarisse Audigier-Valette  6 , Magali Roa  7 , Isabelle Nicolle  8 , Helene Doubre  9 , Nicolas Cloarec  10 , Régine Lamy  11 , Hugues Morel  12 , Hubert Curcio  13 , Aurélie Lagrange  14 , Roland Schott  15 , Marielle Sabatini  16 , Anne Claire Toffart  17 , Julian Pinsolle  18 , Jaafar Bennouna  19 , Christos Chouaid  2 , Julien Mazieres  20
Affiliations
Multicenter Study

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

Jean Mourlanette et al. Target Oncol. 2025 Mar.

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.

PubMed Disclaimer

Conflict of interest statement

Declarations. Author contribution: Jean Mourlanette, Julien Mazieres, and Siham Mallah wrote this article, centered the data in Toulouse, and made statistical analyses. Gaelle Rousseau-Bussac and Christos Chouaid promoted the study, and helped retrieving data. All co authors participated in data collection. Funding: No external funding was used in the preparation of this article. Conflict of interest: All authors were asked to make their statement of potential conflicts of interest on the site https://coi.asco.org/ . Jean Mourlanette, Gaelle Rousseau-Bussac, Siham Mallah, Florian Guisier, Gerard Zalcman, Rémi Veillon, Clarisse Audigier-Valette, Magali Roa, Isabelle Nicolle, Helene Doubre, Nicolas Cloarec, Régine Lamy, Hugues Morel, Hubert Curcio, Aurélie Lagrange, Roland Schott, Marielle Sabatini, Anne Claire Toffart, Julian Pinsolle, Jaafar Bennouna, Christos Chouaid, and Julien Mazieres declare that they have no conflicts of interest that might be relevant to the contents of this article. Ethics Approval: The ethics committee of the Société de Pneumologie de Langue Française approved the study (number: CEPRO 2021-002). Consent to Participate: Not applicable, a letter of information was given to patients alive. Consent to Publish: Not applicable. Availability of Data and Materials: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Code Availability: Not applicable.

Figures

Fig. 1
Fig. 1
Progression-free survival with brigatinib for all patients (A) and for patients with brain metastasis before introducing brigatinib (B). CI confidence interval, mo months
Fig. 2
Fig. 2
Overall survival with brigatinib in all patients since brigatinib introduction
Fig. 3
Fig. 3
Comparison of the three largest series performed in patients with ROS1 metastatic NSCLC under treatment with brigatinib who had crizotinib resistance. NSCLC non-small-cell lung cancer, ORR objective response rate, PFS progression-free survival
See this image and copyright information in PMC

References

    1. Ou S-HI, Tan J, Yen Y, Soo RA. ROS1 as a ‘druggable’ receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway. Expert Rev Anticancer Ther. 2012;12(4):447–56. - PubMed
    1. Stumpfova M, Jänne PA. Zeroing in on ROS1 Rearrangements in Non-Small Cell Lung Cancer. Clin Cancer Res. 2012;18(16):4222–4. - PubMed
    1. Bergethon K, Shaw AT, Ou S-HI, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863–70. - PMC - PubMed
    1. Lindeman NI, Cagle PT, Aisner DL, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the college of american pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018;20(2):129–59. - PubMed
    1. Shaw AT, Riely GJ, Bang Y-J, et al. Crizotinib in ROS1-rearranged advanced non- small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019;30(7):1121–6. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources