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DOI: 10.1055/s-0045-1801883
Safety of Lorlatinib in Patients with Unresectable Advanced ALK-Positive Non-Small-Cell Lung Cancer Previously Treated with ALK Inhibitors: A Single-Arm, Open-Label, Phase IV Study in India
Funding The study was sponsored by Pfizer.
Abstract
Lorlatinib is approved in India for patients with previously treated anaplastic lymphoma kinase (ALK)–positive advanced or recurrent non-small-cell lung cancer (NSCLC). Owing to the limited number of Indian patients in phase I/II and III studies, a postapproval study was conducted to report the safety and efficacy of lorlatinib in this patient population. In this phase IV study, patients with unresectable advanced and/or recurrent ALK-positive NSCLC resistant or intolerant to ≥1 prior ALK inhibitor were treated with lorlatinib. The primary endpoint was investigator-assessed incidence of treatment-related adverse events (TRAEs). Secondary endpoints were investigator-assessed objective response rate (ORR), intracranial ORR, duration of response (DOR), and intracranial DOR. Among the 100 patients enrolled, the most frequently reported TRAEs were hypertriglyceridemia (57%), hypercholesterolemia (57%), and weight increase (38%). The confirmed ORR and intracranial ORR by the investigator were 41% (95% confidence interval [CI]: 31.9–50.8%) and 36% (95% CI: 24.5–48.8%), respectively. The median systemic and intracranial DORs were not reached. The safety profile of lorlatinib was consistent with that reported in the phase I/II study. Lorlatinib showed a clinically meaningful improvement in ORR and intracranial ORR in patients with unresectable advanced ALK-positive NSCLC. These results support the use of lorlatinib in India for patients with previously treated ALK-positive advanced NSCLC.
ClinicalTrials.gov identifier: NCT04541706.
Data Sharing Statement
Upon request and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.
Authorship Statement
This manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author states that the manuscript represents honest work. This manuscript, including related data and tables, has not been published previously and is not under consideration elsewhere.
Patient's Consent
Written informed consent was obtained from all the patients.
Authors' Contributions
U.B., V.G.G., N.R., T.P., H.P., N.G., A.P., C.D., S.B., M.J., and B.B. collected the data. C.R.R., Sh.P., S.P., F.T., and H.T. contributed to the study concept and design and analyzed the data. C.R.R. performed the statistical analysis. All the authors contributed to the interpretation of the data and to the development and approval of the manuscript.
Publikationsverlauf
Artikel online veröffentlicht:
25. Februar 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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