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Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation

Treatment of ALK-rearranged non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) is challenged by the almost inevitable emergence of therapeutic resistance. Different profiles of resistance mechanisms have been reported for the currently available ALK TKIs. The ALK C1156Y mutati...

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Autores principales: Rao, Chuangzhou, Nie, Liangqin, Wu, Xiaokang, Miao, Xiaobo, Chen, Ting, Chen, Liuxi, Zhang, Dongqing, Lin, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530790/
https://www.ncbi.nlm.nih.gov/pubmed/36203454
http://dx.doi.org/10.3389/fonc.2022.915502
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author Rao, Chuangzhou
Nie, Liangqin
Wu, Xiaokang
Miao, Xiaobo
Chen, Ting
Chen, Liuxi
Zhang, Dongqing
Lin, Quan
author_facet Rao, Chuangzhou
Nie, Liangqin
Wu, Xiaokang
Miao, Xiaobo
Chen, Ting
Chen, Liuxi
Zhang, Dongqing
Lin, Quan
author_sort Rao, Chuangzhou
collection PubMed
description Treatment of ALK-rearranged non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) is challenged by the almost inevitable emergence of therapeutic resistance. Different profiles of resistance mechanisms have been reported for the currently available ALK TKIs. The ALK C1156Y mutation is reported in 2% of patients with acquired resistance to crizotinib. A rare substitution at the same site, C1156F, remains largely unknown. Existing evidence includes identification of C1156F and G1202R in an alectinib-resistant patient and sensitivity to crizotinib and resistance to later-generation 3ALK inhibitors in preclinical models. In this report, we present two cases in which NSCLC patients acquired the ALK C1156F mutation on crizotinib monotherapy. Both patients were men, and one had been heavily treated with chemotherapeutic regimens before identification of ALK rearrangement, whereas the other received crizotinib as first-line treatment. Genomic profiling of blood biopsies after progression on crizotinib suggested emergence of the ALK C1156F variant. Both patients subsequently received and responded favorably to alectinib, achieving respective progression-free survival of 21 and 15 months as of the latest follow-ups. To the best of our knowledge, this work is the first to provide clinical evidence of resistance to crizotinib and sensitivity to alectinib in NSCLC patients harboring acquired ALK C1156F mutation.
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spelling pubmed-95307902022-10-05 Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation Rao, Chuangzhou Nie, Liangqin Wu, Xiaokang Miao, Xiaobo Chen, Ting Chen, Liuxi Zhang, Dongqing Lin, Quan Front Oncol Oncology Treatment of ALK-rearranged non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) is challenged by the almost inevitable emergence of therapeutic resistance. Different profiles of resistance mechanisms have been reported for the currently available ALK TKIs. The ALK C1156Y mutation is reported in 2% of patients with acquired resistance to crizotinib. A rare substitution at the same site, C1156F, remains largely unknown. Existing evidence includes identification of C1156F and G1202R in an alectinib-resistant patient and sensitivity to crizotinib and resistance to later-generation 3ALK inhibitors in preclinical models. In this report, we present two cases in which NSCLC patients acquired the ALK C1156F mutation on crizotinib monotherapy. Both patients were men, and one had been heavily treated with chemotherapeutic regimens before identification of ALK rearrangement, whereas the other received crizotinib as first-line treatment. Genomic profiling of blood biopsies after progression on crizotinib suggested emergence of the ALK C1156F variant. Both patients subsequently received and responded favorably to alectinib, achieving respective progression-free survival of 21 and 15 months as of the latest follow-ups. To the best of our knowledge, this work is the first to provide clinical evidence of resistance to crizotinib and sensitivity to alectinib in NSCLC patients harboring acquired ALK C1156F mutation. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530790/ /pubmed/36203454 http://dx.doi.org/10.3389/fonc.2022.915502 Text en Copyright © 2022 Rao, Nie, Wu, Miao, Chen, Chen, Zhang and Lin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Rao, Chuangzhou
Nie, Liangqin
Wu, Xiaokang
Miao, Xiaobo
Chen, Ting
Chen, Liuxi
Zhang, Dongqing
Lin, Quan
Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
title Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
title_full Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
title_fullStr Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
title_full_unstemmed Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
title_short Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation
title_sort case report: durable response to alectinib in alk-rearranged lung adenocarcinoma with acquired, crizotinib-resistant alk c1156f mutation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530790/
https://www.ncbi.nlm.nih.gov/pubmed/36203454
http://dx.doi.org/10.3389/fonc.2022.915502
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