Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)

Background Tivantinib is a non-ATP competitive inhibitor of c-MET receptor tyrosine kinase that may have additional cytotoxic mechanisms including tubulin inhibition. Prostate cancer demonstrates higher c-MET expression as the disease progresses to more advanced stages and to a castration resistant state. Methods 80 patients (pts) with asymptomatic or minimally symptomatic mCRPC were assigned (2:1) to either tivantinib 360 mg PO BID or placebo (P). The primary endpoint was progression free survival (PFS). Results Of the 80 pts. enrolled, 78 (52 tivantinib, 26 P) received treatment and were evaluable. Median follow up is 8.9 months (range: 2.3 to 19.6 months). Patients treated with tivantinib had significantly better PFS vs. those treated with placebo (medians: 5.5 mo vs 3.7 mo, respectively; HR = 0.55, 95% CI: 0.33 to 0.90; p = 0.02). Grade 3 febrile neutropenia was seen in 1 patient on tivantinib while grade 3 and 4 neutropenia was recorded in 1 patient each on tivantinib and placebo. Grade 3 sinus bradycardia was recorded in two men on the tivantinib arm. Conclusions Tivantinib has mild toxicity and improved PFS in men with asymptomatic or minimally symptomatic mCRPC.

Investigational new drugs. 2018 Aug 07 [Epub ahead of print]

Paul Monk, Glenn Liu, Walter M Stadler, Susan Geyer, Ying Huang, John Wright, Miguel Villalona-Calero, James Wade, Russell Szmulewitz, Shilpa Gupta, Amir Mortazavi, Robert Dreicer, Roberto Pili, Nancy Dawson, Saby George, Jorge A Garcia

Ohio State University, A433b Starling-Loving Hall, 310 W. 10th ave, Columbus, OH, 43082, USA. ., University of Wisconsin Carbone Cancer Center, 1111 Highland Ave, Madison, WI, 53705, USA., University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA., University of South Florida, 4202 E Fowler Ave, Tampa, FL, 33620, USA., Ohio State University, 320 W 10th Ave, Columbus, OH, 43210-1280, USA., National Cancer Institute, 9609 Medical Center Dr., MSC, Bethesda, MD, 9739, USA., Miami Cancer Institute, 8900 N Kendall Dr, Miami, FL, 33176-2118, USA., Cancer Care Specialists of Central Illinois, 210 W Mckinley Ave, Decatur, IL, 62526, USA., University of Chicago Medical Center, 5841 S Maryland Ave # MC2115, Chicago, IL, 60637-1447, USA., University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455-0341, USA., University of Virginia School of Medicine, PO Box 800716, Charlottesville, VA, 22908-0716, USA., Indiana University, 535 Barnhill Drive, Indianapolis, IN, 46202, USA., Georgetown-Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd NW, Washington, DC, 20007-2113, USA., Roswell Park Cancer Institute, 6 Symphony Cir, Orchard Park, NY, 14127, USA., Taussig Cancer Institute, 9500 Euclid Ave, Cleveland, OH, 44195-0001, USA.