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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 12/2020

01-12-2020 | NSCLC | Research Article

Clinical activity of brigatinib in ROS1-rearranged non-small cell lung cancer

Authors: E. Dudnik, A. Agbarya, R. Grinberg, A. Cyjon, J. Bar, M. Moskovitz, N. Peled, the Israel Lung Cancer Group

Published in: Clinical and Translational Oncology | Issue 12/2020

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Abstract

Background

Brigatinib is a potent ROS1 inhibitor. The existing data on its clinical activity in ROS1-rearranged non-small cell lung cancer (NSCLC) are limited to four cases.

Methods

Six patients with ROS1-rearranged advanced NSCLC treated with brigatinib were identified through search of the internal databases of four participating cancer centers. Four additional patients were selected by PubMed and Google Scholar search. The objective response rate (ORR), progression-free survival (PFS) (RECIST v.1.1), duration of treatment (DOT), and safety were assessed.

Results

Of eight patients evaluable for response assessment (crizotinib naive-1, crizotinib resistant -7), three patients demonstrated a partial response (ORR-37%). One crizotinib-naive patient had an ongoing response at 21.6 months. Of seven crizotinib-resistant patients, two patients demonstrated a partial response (ORR-29%), and one patient (14%) had stable disease. PFS, available in four crizotinib-resistant patients, was 7.6 + , 2.9, 2.0, and 0.4 months. In crizotinib-resistant patients, DOT was 9.7 + , 7.7 + , 7.6 + , 4.0, 2.0, 1.1, 0.4 months, and was not reported in two patients. Genomic profiling in one responder revealed no ROS1 alteration, suggesting that the response was attributable to “off-target” brigatinib activity. In two patients with progressive disease, genomic profiling demonstrated a cMET exon 14 mutation + KRAS G12A mutation in one case, and a persisting ROS1-CD74 fusion + TP53 K139N, FGFR2 E250G, ATM G2695D, and NF1 R2258Q mutations in the other. No grade 3–5 toxicity was observed.

Conclusion

Brigatinib demonstrated modest activity in crizotinib-resistant ROS1-rearranged NSCLC. Its intracranial and systemic activity should be assessed in correlation with the underlying molecular mechanism of crizotinib resistance.
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Metadata
Title
Clinical activity of brigatinib in ROS1-rearranged non-small cell lung cancer
Authors
E. Dudnik
A. Agbarya
R. Grinberg
A. Cyjon
J. Bar
M. Moskovitz
N. Peled
the Israel Lung Cancer Group
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 12/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-020-02376-w

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