Randomized phase 2 study of tivantinib plus erlotinib versus single-agent chemotherapy in previously treated KRAS mutant advanced non-small cell lung cancer

•Combination of the MET inhibitor tivantinib and erlotinib is feasible.•In advanced KRAS mutant NSCLC, erlotinib-tivantinib has similar PFS as chemotherapy.•The most common toxicities of erlotinib-tivantinib are rash and diarrhea.•National screening platforms support enrollment of molecular subsets...

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Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2018-03, Vol.117, p.44-49
Main Authors: Gerber, David E., Socinski, Mark A., Neal, Joel W., Wakelee, Heather A., Shirai, Keisuke, Sequist, Lecia V., Rosovsky, Rachel P., Lilenbaum, Rogerio C., Bastos, Bruno R., Huang, Chao, Johnson, Melissa L., Hesketh, Paul J., Subramaniam, Deepa S., Dietrich, Martin F., Chai, Feng, Wang, Yunxia, Kazakin, Julia, Schwartz, Brian, Schiller, Joan H., Brahmer, Julie R., Kelly, Ronan J.
Format: Article
Language:English
Subjects:
Adenocarcinoma
MET
Small molecule
Targeted therapy
Tyrosine kinase inhibitor
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Summary:•Combination of the MET inhibitor tivantinib and erlotinib is feasible.•In advanced KRAS mutant NSCLC, erlotinib-tivantinib has similar PFS as chemotherapy.•The most common toxicities of erlotinib-tivantinib are rash and diarrhea.•National screening platforms support enrollment of molecular subsets to clinical trials. KRAS mutations are identified in approximately 25% of non-small cell lung cancer (NSCLC) cases and are associated with resistance to currently available targeted therapies. The MET oncogene may be implicated in malignant progression of KRAS-mutant tumors. In a pre-specified subset analysis of KRAS mutant cancers in an earlier phase 2 study of erlotinib plus the oral MET inhibitor tivantinib, combination therapy was associated with substantial clinical benefit compared to erlotinib alone (progression-free survival [PFS] HR 0.18; P 
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2018.01.010