Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with -Mutated Hepatocellular Carcinoma.
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BORIS DOI
Date of Publication
October 1, 2018
Publication Type
Article
Division/Institute
Author
Lim, Ho Yeong | |
Merle, Philippe | |
Weiss, Karl Heinz | |
Yau, Thomas | |
Ross, Paul | |
Mazzaferro, Vincenzo | |
Blanc, Jean-Frédéric | |
Ma, Yuk Ting | |
Yen, Chia Jui | |
Kocsis, Judit | |
Choo, Su Pin | |
Sukeepaisarnjaroen, Wattana | |
Gérolami, René | |
Gane, Edward J | |
Ryoo, Baek-Yeol | |
Peck-Radosavljevic, Markus | |
Dao, Thong | |
Yeo, Winnie | |
Lamlertthon, Wisut | |
Thongsawat, Satawat | |
Teufel, Michael | |
Roth, Katrin | |
Reis, Diego | |
Childs, Barrett H | |
Krissel, Heiko | |
Llovet, Josep M |
Subject(s)
Series
Clinical cancer research
ISSN or ISBN (if monograph)
1078-0432
Publisher
American Association for Cancer Research
Language
English
Publisher DOI
PubMed ID
29950351
Description
Refametinib, an oral MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in patients with -mutated hepatocellular carcinoma (HCC). Two phase II studies evaluated the efficacy of refametinib monotherapy and refametinib plus sorafenib in patients with -mutant unresectable or metastatic HCC. Eligible patients with mutations of cell-free circulating tumor DNA (ctDNA) determined by beads, emulsion, amplification, and magnetics technology received twice-daily refametinib 50 mg ± sorafenib 400 mg. Potential biomarkers were assessed in ctDNA via next-generation sequencing (NGS). Of 1,318 patients screened, 59 (4.4%) had a mutation, of whom 16 received refametinib and 16 received refametinib plus sorafenib. With refametinib monotherapy, the objective response rate (ORR) was 0%, the disease control rate (DCR) was 56.3%, overall survival (OS) was 5.8 months, and progression-free survival (PFS) was 1.9 months. With refametinib plus sorafenib, the ORR was 6.3%, the DCR was 43.8%, OS was 12.7 months, and PFS was 1.5 months. In both studies, time to progression was 2.8 months. Treatment-emergent toxicities included fatigue, hypertension, and acneiform rash. Twenty-seven patients had ctDNA samples available for NGS. The most frequently detected mutations were in (63.0%), (48.1%), and β-catenin (; 37.0%). Prospective testing for family mutations using ctDNA was a feasible, noninvasive approach for large-scale mutational testing in patients with HCC. A median OS of 12.7 months with refametinib plus sorafenib in this small population of -mutant patients may indicate a synergistic effect between sorafenib and refametinib-this preliminary finding should be further explored.
File(s)
File | File Type | Format | Size | License | Publisher/Copright statement | Content | |
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1078-0432.CCR-17-3588.full.pdf | text | Adobe PDF | 750.9 KB | publisher | published |