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Multicenter retrospective analysis of the safety and efficacy of regorafenib after progression on sorafenib in Korean patients with hepatocellular carcinoma

Published on Jun 1, 2019in Investigational New Drugs2.663
· DOI :10.1007/s10637-018-0707-5
Changhoon Yoo16
Estimated H-index: 16
(UOU: University of Ulsan),
Joong Won Park24
Estimated H-index: 24
+ 6 AuthorsHo Yeong Lim25
Estimated H-index: 25
(SKKU: Sungkyunkwan University)
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Abstract
Background The pivotal RESORCE trial showed that regorafenib was effective as second-line therapy for patients with advanced HCC who progressed on first-line sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. Methods Between April 2017 and August 2017, the Named Patient Program (NPP) was activated to provide controlled, pre-approval access of regorafenib in Korea. This analysis is a multicenter retrospective study of patients who received regorafenib under the NPP. Results A total of 49 patients entered into this NPP, and 40 patients received regorafenib in five Korean institutions. All but one patient received regorafenib as second-line therapy after progression on sorafenib, and 36 (90%) and 34 (85%) patients were classified as Child-Pugh A and BCLC stage C, respectively. The response rate was 10% (n = 4). The median progression-free survival (PFS) was 3.7 months (95% CI, 2.5–4.9 months), and the median overall survival (OS) was not reached. The 1 year OS rate was 54.6%. The time-to-progression (TTP) on prior sorafenib was significantly associated with PFS and OS. The most common grade 3–4 toxicities were hand-foot skin reaction (n = 3, 8%), hypertension (n = 2, 5%), and increased aspartate aminotransferase (n = 2, 5%). Conclusion Regorafenib was well-tolerated and effective in patients with advanced HCC who progressed on first-line sorafenib, with efficacy and safety outcomes consistent with those of the previous RESORCE trial. TTP on first-line sorafenib may predict the efficacy of subsequent regorafenib.
  • References (15)
  • Citations (2)
References15
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#2Philippe MerleH-Index: 28
Last. Jordi Bruix (University of Barcelona)H-Index: 93
view all 17 authors...
Background & Aims The RESORCE trial showed that regorafenib improves overall survival (OS) in patients with hepatocellular carcinoma progressing during sorafenib treatment (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.50–0.78; p Methods In RESORCE, 573 patients were randomized 2:1 to regorafenib 160 mg/day or placebo for 3 weeks on/1 week off. Efficacy and safety were evaluated by last sorafenib dose. The time from the start of sorafenib to death was assessed. Time to progression (TTP)...
40 CitationsSource
#1Ghassan K. Abou-Alfa (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 35
#2Tim Meyer (UCL: University College London)H-Index: 40
Last. R. Kate Kelley (UCSF: University of California, San Francisco)H-Index: 33
view all 22 authors...
Abstract Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...
174 CitationsSource
#1Andrew X Zhu A X (Harvard University)H-Index: 66
#2Richard S. Finn (UCLA: University of California, Los Angeles)H-Index: 52
Last. Tatsuya YamashitaH-Index: 36
view all 59 authors...
Summary Background Immune checkpoint blockade therapy has shown promising results in patients with advanced hepatocellular carcinoma. We aimed to assess the efficacy and safety of pembrolizumab in this patient population. Methods KEYNOTE-224 is a non-randomised, multicentre, open-label, phase 2 trial that is set in 47 medical centres and hospitals across ten countries. Eligible patients had pathologically confirmed hepatocellular carcinoma; had previously been treated with sorafenib and were eit...
159 CitationsSource
#1Maria KisselH-Index: 2
#2Sandra BerndtH-Index: 1
Last. Dieter ZopfH-Index: 6
view all 10 authors...
// Maria Kissel 1 , Sandra Berndt 2 , Lukas Fiebig 1 , Simon Kling 3 , Qunsheng Ji 4 , Qingyang Gu 4 , Tina Lang 5 , Frank-Thorsten Hafner 1 , Michael Teufel 6 and Dieter Zopf 2 1 Drug Discovery, Bayer AG, Wuppertal, Germany 2 Drug Discovery, Bayer AG, Berlin, Germany 3 Biochemistry, NMI Natural and Medicinal Sciences Institute, University of Tubingen, Reutlingen, Germany 4 Research Service Division, Oncology & Immunology Unit, WuXi AppTec Co. Ltd., Shanghai, China 5 Research & Clinical Sciences...
14 CitationsSource
#2Bruno Sangro (University of Navarra)H-Index: 56
Last. Ignacio Melero Bermejo (CIMA: Chartered Institute of Management Accountants)H-Index: 56
view all 21 authors...
Summary Background For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. Methods We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18...
609 CitationsSource
#1Yokosuka OsamuH-Index: 1
#2Meinhardt GeroldH-Index: 1
Last. Jordi BruixH-Index: 1
view all 3 authors...
1 Citations
#1Jordi Bruix (University of Barcelona)H-Index: 93
#2Shukui QinH-Index: 28
Last. Guohong Han (Fourth Military Medical University)H-Index: 30
view all 24 authors...
Summary Background There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. Methods In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafe...
632 CitationsSource
1 CitationsSource
#1MasatoshiKudo (Kindai University)H-Index: 75
#2Riccardo Lencioni (UniPi: University of Pisa)H-Index: 62
Last. Sheng Long Ye (Fudan University)H-Index: 10
view all 18 authors...
Background & Aims Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib. Methods GIDEON ...
26 CitationsSource
#1Lotfi Abou-Elkacem (RWTH Aachen University)H-Index: 3
#2Susanne Arns (RWTH Aachen University)H-Index: 9
Last. Wiltrud Lederle (RWTH Aachen University)H-Index: 21
view all 7 authors...
The combination of target-specific drugs like bevacizumab with chemotherapeutics has improved treatment efficacy in advanced colorectal cancer (CRC). However, the clinical prognosis of metastatic CRCs is still poor, and novel drugs are currently assessed with respect to their efficacies in patients with CRCs. In a phase III study, the multikinase inhibitor regorafenib (BAY 73-4506) has recently been shown to prolong survival of patients with CRCs after standard therapies failed. In the present s...
82 CitationsSource
Cited By2
Newest
#1Sadahisa Ogasawara (Chiba University)H-Index: 16
#2Yoshihiko Ooka (Chiba University)H-Index: 15
Last. Naoya Kato (Chiba University)H-Index: 8
view all 32 authors...
Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on ...
1 CitationsSource
#1Sadahisa OgasawaraH-Index: 16
#2Yoshihiko OokaH-Index: 15
Last. Naoya KatoH-Index: 38
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In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TA...
Source
#1Antonio FacciorussoH-Index: 17
#2Mohamed A. Abd El Aziz (UA: University of Arizona)H-Index: 1
Last. Rodolfo SaccoH-Index: 20
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Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model a...
1 CitationsSource
#1Wan WangH-Index: 2
#2Kaoru TsuchiyaH-Index: 25
Last. Namiki IzumiH-Index: 48
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Background: We aimed to explore the relative dose intensity (RDI) and post-regorafenib treatments in regorafenib therapy. Methods: The medical records of 38 patients treated with regorafenib between July 2017 and June 2019 at our institution were collected. The RDI of regorafenib for the first month (1M-RDI) was calculated. Results: The overall survival (OS) and progression-free survival (PFS) were 12.4 and 3.7 months. The objective response rate and disease control rate were 13.2% and 71.1%. Th...
3 CitationsSource