Abstract
The treatment for anaplastic lymphoma kinase (ALK)‐positive lung cancer has been rapidly evolving since the introduction of several ALK tyrosine kinase inhibitors (ALK‐TKI) in clinical practice. However, the acquired resistance to these drugs has become an important issue. In this study, we collected a total of 112 serial biopsy samples from 32 patients with ALK‐positive lung cancer during multiple ALK‐TKI treatments to reveal the resistance mechanisms to ALK‐TKI. Among 32 patients, 24 patients received more than two ALK‐TKI. Secondary mutations were observed in 8 of 12 specimens after crizotinib failure (G1202R, G1269A, I1171T, L1196M, C1156Y and F1245V). After alectinib failure, G1202R and I1171N mutations were detected in 7 of 15 specimens. G1202R, F1174V and G1202R, and P‐gp overexpression were observed in 3 of 7 samples after ceritinib treatment. L1196M + G1202R, a compound mutation, was detected in 1 specimen after lorlatinib treatment. ALK‐TKI treatment duration was longer in the on‐target treatment group than that in the off‐target group (13.0 vs 1.2 months). In conclusion, resistance to ALK‐TKI based on secondary mutation in this study was similar to that in previous reports, except for crizotinib resistance. Understanding the appropriate treatment matching resistance mechanisms contributes to the efficacy of multiple ALK‐TKI treatment strategies.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.