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. 2025 Jun;12(2):227-235.
doi: 10.1007/s40801-025-00484-z. Epub 2025 Feb 26.

Safety and Effectiveness of Brigatinib in Anaplastic Lymphoma Kinase (ALK) Positive Metastatic Non-Small Cell Lung Cancer (NSCLC) in Argentina: A Post-Marketing Surveillance Study

Claudio Martin  1   2 , Gabriela Ileana Malcervelli  3 , Gastón Lucas Martinengo  4 , Patricio Levit  5 , Patricio Servienti  6   7 , Elisa Malaver  8 , Laura Brion  9 , Vanesa Patronella  9 , Andrea Zumárraga  10 , Jose Zarba  11   12
Affiliations

Safety and Effectiveness of Brigatinib in Anaplastic Lymphoma Kinase (ALK) Positive Metastatic Non-Small Cell Lung Cancer (NSCLC) in Argentina: A Post-Marketing Surveillance Study

Claudio Martin et al. Drugs Real World Outcomes. 2025 Jun.

Abstract

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor was licensed for the treatment of ALK-positive metastatic non-small cell lung cancer in 2016. However, real-world evidence on the safety and effectiveness of brigatinib in Latin America remains limited.

Objective: The aim of this study was to assess the safety and effectiveness of brigatinib in the real world in Argentina.

Methods: We conducted a non-interventional cohort study of adult patients (aged ≥ 18 years) with a diagnosis of ALK-positive metastatic non-small cell lung cancer not previously treated (first line) or previously treated (second line) with an ALK inhibitor and who received at least one dose of brigatinib between November 2020 and March 2023. The primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes at the 24-week follow-up were the percentage of patients with an overall best objective response rate of complete or partial response; intracranial objective response rate; progression-free survival; and overall survival.

Results: Of the 39 patients included in the study (n = 22 [first line]; n = 17 [second line]), 12 patients (30.7%) experienced treatment-emergent adverse events, with the most frequent being increased levels of transaminases (7.6%), increased level of blood creatine phosphokinase (5%) and hypokalaemia (5%). Most adverse events (85.7%) were mild to moderate. Effectiveness outcomes at 24 weeks in patients treated with brigatinib first line or second line, respectively, were as follows: overall objective response rate: 81.8% and 70.5%; intracranial objective response rate (in patients with brain metastases at baseline): 66.6% and 88.8%; progression-free survival: 93.8% and 82.4%; overall survival: 100% and 87.5%.

Conclusions: Brigatinib was demonstrated to be a safe and effective treatment option for ALK-positive metastatic non-small cell lung cancer in routine clinical practice in Argentina.

Clinical trial registration: NCT04887519.

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Conflict of interest statement

Declarations. Funding: This study was supported by Takeda Argentina S.A. Conflicts of Interest/Competing Interests: Claudio Martin received consulting fees from Pfizer, Astra Zeneca, Takeda, Boehringer Ingelheim and Roche. Gabriela Ileana Malcervelli received travel support and consulting fees from Takeda. Lucas Gastón Martinengo has no conflict of interest that are directly relevant to the content of this article. Patricio Servienti received travel support from Raffo, GSK, Takeda, Merck, BMS and Pfizer; lecture fees from GSK and Raffo; and consulting fees from Pfizer. Patricio Levit received lectures fees from Roche, Takeda and AstraZeneca, and consulting fees from Tuteur. Elisa Malaver, Laura Brion, Vanesa Patronella and Andrea Zumarrága are employees of Takeda Argentina S.A. Jose Zarba received travel support from MSD, BMS and Takeda; lecture fees from Novartis, BMS and MSD; and consulting fees from MSD, Takeda and AstraZeneca. Ethics Approval: The study protocol (Brigatinib-5008) was approved by an independent ethics committee (Fundación de Estudios Farmacológicos y Medicamentos, FEFyM) on 21 October, 2020. All patients were required to provide mandatory written informed consent. Good pharmacoepidemiology practice guidelines, local applicable regulations and the Declaration of Helsinki were followed. Furthermore, this study conformed to all regulations concerning the use of personal data. The study was incorporated in the clinical study registry of the city of Buenos Aires, Argentina (PRIISA-BA #3201) and in ClinicalTrials.gov (NCT04887519). Consent to Participate: To receive brigatinib during the post-marketing surveillance study period, eligible patients were required to provide a written inform consent in the presence of the treating physician. The patients were informed about the medication and the scope of the study before providing their consent. Consent for Publication: Not applicable. Availability of Data and Material: The datasets, including the redacted study protocol, redacted statistical analysis plan and individual participant data supporting the results reported in this article, will be made available within 3 months from initial request to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization. Code Availability: Not applicable. Authors’ Contributions: CM, GIM, LGM, PS, PL and JZ participated in patient recruitment and data collection. EM, LB, VP, AZ and JZ participated in study design. All authors participated in the analysis and interpretation of data and contributed to writing and critical revision of all drafts.

Figures

Fig. 1
Fig. 1
Patient flowchart and disposition
See this image and copyright information in PMC

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