| General information |
| Database: | DB00124 |
| Objective: | Tivantinib (ARQ 197) has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. they aimed to assess efficacy and safety of tivantinib for secondline treatment of advanced hepatocellular carcinoma. |
| Authors: | Santoro A, et al |
| Title: | Tivantinib for secondline treatment of advanced hepatocellular carcinoma: a randomised, placebocontrolledphase 2 study. |
| Journal: | Lancet Oncol |
| Year: | 2013 |
| PMID: | 23182627 |
| Trial Design |
| Clinical Trial Id: | NCT00988741 |
| Agent: | tivantinib
|
| Target: | Protooncogene cMet
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma not amenable to surgical or regional therapies |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a completed, multicentre, randomised, placebocontrolled, doubleblind, phase II study |
| Key Patients Feature: | patients with advanced hepatocellular carcinoma and ChildPugh A cirrhosis who had progressed on or were unable to tolerate firstline systemic therapy. |
| Biomarker: | MET expression |
| Biomark Analysis: | For patients with METhigh tumours, median time to progression was longer with tivantinib than for those on placebo (2.7 months [95% CI 1.48.5] for 22 METhigh patients on tivantinib vs 1.4 months [1.41.6] for 15 METhigh patients on placebo; HR 0.43, 95% CI 0.190.97; p=0.03). |
| Control Group Info: | placebo:38 at 360 mg twicedaily and 33 at 240 mg twicedaily;36 patients were randomly assigned to receive placebo |
| Treatment Info: | randomly allocated patients 2:1 to receive tivantinib (360 mg twicedaily) or placebo until disease progression. The tivantinib dose was amended to 240 mg twicedaily because of high incidence of treatmentemergent grade 3 or worse neutropenia. |
| Primary End Point: | time to progression, according to independent radiological review in the intentiontotreat population and assessed tumour samples for MET expression with immunohistochemistry (high expression was regarded as more than and equal to 2+ in more than and equal to 50% of tumour cells). |
| Secondary End Point: | NA |
| Patients Number: | 107 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 46 (65%) patients in the tivantinib group and 26 (72%) of those in the placebo group had progressive disease. |
| Median Time to Progression: | TTP was longer for patients treated with tivantinib (1.6 months) than placebo (1.4 months, HR 0.64, 90% CI 0.430.94; p=0.04). For patients with METhigh tumours, median TTP was longer with tivantinib than for those on placebo:2.7 months for 22 METhigh patients on tivantinib vs 1.4 months for 15 METhigh patients on placebo; HR 0.43, 95% CI 0.190.97; p=0.03). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common grade 3 or worse adverse events in the tivantinib group were neutropenia (ten patients [14%] vs none in the placebo group) and anaemia (eight [11%] vs none in the placebo group). Eight patients (21%) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two (6%) patients in the 240 mg group. Four deaths related to tivantinib occurred from severe neutropenia. 24 (34%) patients in the tivantinib group and 14 (39%) patients in the placebo group had serious adverse events. |
| Conclusions: | Tivantinib could provide an option for secondline treatment of patients with advanced hepatocellular carcinoma and wellcompensated liver cirrhosis, particularly for patients with METhigh tumours. Confirmation in aphase 3 trial is needed, with a starting dose of tivantinib 240 mg twicedaily. |