期刊
CLINICAL COLORECTAL CANCER
卷 18, 期 2, 页码 125-+出版社
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clcc.2019.02.004
关键词
Advanced colon cancer; Anti-EGFR; Molecular selection; New therapeutic strategy
类别
资金
- Humanitas Clinical and Research Center
- Daiichi Sankyo
There is a major need for therapeutic strategies able to overcome resistance to available treatments for patients with metastatic colorectal cancer. In this phase II study, we evaluated the combination of tivantinib and cetuximab in 41 molecularly selected patients with acquired resistance to anti-epidermal growth factor receptors and MET overexpression. Overall, our results suggest that this combination is not worth of further development. Background: MET overexpression/amplification has been associated with resistance to anti- epidermal growth factor receptor therapies in patients with metastatic colorectal cancer (mCRC). Combining tivantinib, an inhibitor of the MET receptor tyrosine kinase, and cetuximab may be effective in patients with epidermal growth factor receptor-resistant MET-high mCRC. Patients and Methods: This multicenter, single-arm, Simon 2-stage, phase II study enrolled patients with MET-high, KRAS wild-type mCRC, who were treated with >= 1 prior systemic therapy, with at least stable disease on the last treatment regimen containing cetuximab or panitumumab. Patients were enrolled if they presented tumor progression on cetuximab or panitumumab within 3 months before enrollment. Patients received tivantinib (360 mg twice daily) plus cetuximab (500 mg intravenously every 2 weeks). The primary endpoint was objective response rate; secondary endpoints included progression-free survival, overall survival, and safety. The treatment would be considered effective if >= 5 confirmed partial responses were observed among 41 patients. Results: In total, 41 patients were evaluated, 4 patients (9.8%) achieved an objective response, the median progression-free survival was 2.6 months (95% confidence interval, 1.9-4.2 months), and the median overall survival was 9.2 months (95% confidence interval, 7.1-15.1 months). Among 13 patients with tested MET amplification, 2 responding patients had MET amplification compared with none of the nonresponding patients. The most common grade >= 3 treatment-emergent adverse events were neutropenia (14.6%), skin toxicity (12.2%), and fatigue (9.8%). Conclusion: Although the study did not meet its primary endpoint, efficacy results suggest some activity of the tested combination, with almost 10% of patients achieving objective response in a difficult-to-treat setting. Treatment-emergent adverse events were consistent with the known safety profile of tivantinib and cetuximab. (C) 2019 Elsevier Inc. All rights reserved.
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