Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with -Mutated Hepatocellular Carcinoma.

Lim, Ho Yeong and Merle, Philippe and Weiss, Karl Heinz and Yau, Thomas and Ross, Paul and Mazzaferro, Vincenzo and Blanc, Jean-Frédéric and Ma, Yuk Ting and Yen, Chia Jui and Kocsis, Judit and Choo, Su Pin and Sukeepaisarnjaroen, Wattana and Gérolami, René and Dufour, Jean-François and Gane, Edward J and Ryoo, Baek-Yeol and Peck-Radosavljevic, Markus and Dao, Thong and Yeo, Winnie and Lamlertthon, Wisut and Thongsawat, Satawat and Teufel, Michael and Roth, Katrin and Reis, Diego and Childs, Barrett H and Krissel, Heiko and Llovet, Josep M (2018) Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with -Mutated Hepatocellular Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research, 24 (19). pp. 4650-4661. ISSN 1078-0432.

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Official URL: https://clincancerres.aacrjournals.org/content/24/...

Abstract

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. .

Item Type: Article
Subjects: QZ Pathology. Oncology
WH Haemic and lymphatic systems. Haematology
WI Digestive system. Gastroenterology
WK Endocrine system. Endocrinology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Jamie Edgar
Date Deposited: 20 Dec 2019 15:16
Last Modified: 20 Dec 2019 15:16
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2708

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