Randomized phase 2 study of tivantinib plus erlotinib versus single-agent chemotherapy in previously treated KRAS mutant advanced non-small cell lung cancer. (March 2018)

• Record Type: Journal Article
• 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.
• Is Part Of: Lung cancer. Volume 117(2018)
• Page Start: 44
• Page End: 49
• Publication Date: 2018-03
• Subjects: MET -- Adenocarcinoma -- Small molecule -- Tyrosine kinase inhibitor -- Targeted therapy; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.01.010
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: 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. Abstract: Background: 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 < 0.01). The current study was conducted to evaluate this combination further in KRAS mutant non-small cell lung cancer (NSCLC). Materials and methods: Previously treated patients with advanced KRAS mutant NSCLC were randomized to receive either oral tivantinib (360 mg twice daily) plus erlotinib (150 mg daily) (ET) or single-agent chemotherapy (investigator's choice of pemetrexed, docetaxel, or gemcitabine) (C). The primary endpoint was PFS. At progression, crossover from C to ET was permitted. Results: Ninety-six patients were randomly assigned to ET (n = 51) or to C (n = 45). Median PFS was 1.7 months (mos) for ET and 4.3 mos for C (HR 1.19; 95% CI, 0.71-1.97; P = 0.50). There was no difference in overall survival (HR 1.20; 95% CI, 0.76-1.88; P = 0.44). There were 4 partial responses in the C arm, and none in the ET arm. Overall, adverse events occurred more frequently in the C arm, with more cytopenias, nausea, fatigue, and alopecia. Dermatologic toxicities were more common in the ET arm. Conclusion: In previously treated patients with advanced KRAS mutant NSCLC, the combination of the MET inhibitor tivantinib and erlotinib is not superior to conventional single-agent chemotherapy.