Tivantinib does not improve overall survival (OS) among patients with high MET-expressing hepatocellular carcinoma (HCC) previously treated with sorafenib compared with placebo, according to a study published in The Lancet Oncology.1

Previous studies have demonstrated tivantinib — a small-molecule receptor tyrosine kinase inhibitor (TKI) that prevents growth and induces apoptosis in cells that express MET — prolonged progression-free survival (PFS) and OS.

For the phase 3 METIV-HCC study (ClinicalTrials.gov Identifier: NCT01755767), researchers randomly assigned 340 patients with unresectable HCC previously treated with sorafenib to receive placebo or tivantinib 120 mg twice daily. The median follow up was 18.1 months.

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Results showed that the median OS among patients treated with tivantinib was 8.4 months (95% CI, 6.8-10.0) compared with 9.1 months (95% CI, 7.3-10.14) in placebo-receiving patients (hazard ratio [HR], 0.97; 95% CI, 0.75-1.25; P = .81).

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Grade 3 or worse treatment-emergent adverse events (AEs) occurred in 56% compared with 55% of patients who received tivantinib and placebo, respectively; the most commonly reported AEs in the tivantinib arm included ascites, anemia, abdominal pain, and neutropenia.

Twenty-two percent (50) of patients treated with tivantinib compared with 16% (18) of patients treated with placebo died within 30 days of the last dose of the study medication. The most common causes of death in the tivantinib death were hepatic failure and general deterioration. Three patients in the tivantinib arm died due to sepsis, anemia, and acute renal failure, all of which were considered to be treatment-related AEs.

Even though results showed that tivantinib did not improve survival outcomes, the authors concluded that “the study shows the feasibility of doing integral tissue biomarker studies in patients with advanced hepatocellular carcinoma. Additional randomized studies are needed to establish whether MET inhibition could be a potential therapy for some subsets of patients with advanced hepatocellular carcinoma.”


  1. Rimassa L, Assenat E, Peck-Radosavljevic M, et al. Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study [published online April 3, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30146-3