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ID 61391
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Harada, Daijiro Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center
Isozaki, Hideko Department of Clinical Pharmaceutics, Okayama University Hospital
Kozuki, Toshiyuki Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center
Yokoyama, Toshihide Department of Respiratory Medicine, Kurashiki Central Hospital
Yoshioka, Hiroshige Department of Respiratory Medicine, Kurashiki Central Hospital
Bessho, Akihiro Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
Hosokawa, Shinobu Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
Takata, Ichiro Department of Internal Medicine, Fukuyama City Hospital
Hotta, Katsuyuki Department of Respiratory Medicine, Okayama University Hospital Kaken ID publons researchmap
Kiura, Katsuyuki Department of Respiratory Medicine, Okayama University Hospital ORCID Kaken ID publons researchmap
Okayama Lung Cancer Study Group
Abstract
Background
The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC.
Methods
Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest.
Results
Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred.
Conclusions
Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events.
Keywords
Alectinib
anaplastic lymphoma kinase
crizotinib
drug therapy
non-small cell lung carcinoma
Published Date
2021-01-20
Publication Title
Thoracic Cancer
Volume
volume12
Issue
issue5
Publisher
Wiley
Start Page
643
End Page
649
ISSN
1759-7706
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2021 The Authors.
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isVersionOf https://doi.org/10.1111/1759-7714.13825
License
https://creativecommons.org/licenses/by-nc-nd/4.0/