Richard S Finn1, Philippe Merle2, Alessandro Granito3, Yi-Hsiang Huang4, György Bodoky5, Marc Pracht6, Osamu Yokosuka7, Olivier Rosmorduc8, René Gerolami9, Chiara Caparello10, Roniel Cabrera11, Charissa Chang12, Weijing Sun13, Marie-Aude LeBerre14, Annette Baumhauer15, Gerold Meinhardt16, Jordi Bruix17. 1. Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: rfinn@mednet.ucla.edu. 2. Groupement Hospitalier Lyon Nord, Hepatology Unit, Lyon, France. 3. Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. 4. Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 5. Department of Oncology, St Laszlo Teaching Hospital, Budapest, Hungary. 6. Service d'Oncologie Médicale, Centre Eugène Marquis, Rennes, France. 7. Department of Gastroenterology and Nephrology, Chiba University, Chiba, Japan. 8. Department of Gastroenterology and Hepatology, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris and Université Pierre et Marie Curie, Sorbonne Universités, Paris, France. 9. Service d'Hépato-gastroentérologie, CHU Timone, Université de la Méditerranée, Marseille, France. 10. Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 11. University of Florida, Hepatology, UF Health Cancer Center, Gainesville, FL, USA. 12. Liver Cancer Program, Division of Liver Diseases, Mount Sinai Medical Center, New York, NY, USA. 13. Medical Oncology Division, University of Kansas School of Medicine, Kansas City, KS, USA. 14. Bayer HealthCare SAS, Loos, France. 15. Bayer AG, Leverkusen, Germany. 16. Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. 17. BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain. Electronic address: jbruix@clinic.ub.es.
Abstract
BACKGROUND & AIMS: The RESORCE trial showed that regorafenib improves overall survival (OS) in patients with hepatocellular carcinoma progressing duringsorafenib treatment (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.50-0.78; p <0.0001). This exploratory analysis describes outcomes of sequential treatment with sorafenib followed by regorafenib. 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) in RESORCE was analyzed by TTP during prior sorafenib treatment. RESULTS:HRs (regorafenib/placebo) for OS by last sorafenib dose were similar (0.67 for 800 mg/day; 0.68 for <800 mg/day). Rates of grade 3, 4, and 5 adverse events with regorafenib by last sorafenib dose (800 mg/day vs. <800 mg/day) were 52%, 11%, and 15% vs. 60%, 10%, and 12%, respectively. Median times (95% CI) from the start of sorafenib to death were 26.0 months (22.6-28.1) for regorafenib and 19.2 months (16.3-22.8) for placebo. Median time from the start of sorafenib to progression on sorafenib was 7.2 months for the regorafenib arm and 7.1 months for the placebo arm. An analysis of TTP in RESORCE in subgroups defined by TTP during prior sorafenib in quartiles (Q) showed HRs (regorafenib/placebo; 95% CI) of 0.66 (0.45-0.96; Q1); 0.26 (0.17-0.40; Q2); 0.40 (0.27-0.60; Q3); and 0.54 (0.36-0.81; Q4). CONCLUSIONS: These exploratory analyses show that regorafenib conferred a clinical benefit regardless of the last sorafenib dose or TTP on prior sorafenib. Rates of adverse events were generally similar regardless of the last sorafenib dose. LAY SUMMARY: This analysis examined characteristics and outcomes of patients with hepatocellular carcinoma who were treated with regorafenib after they had disease progression during sorafenib treatment. Regorafenib provided clinical benefit to patients regardless of the pace of their disease progression during prior sorafenib treatment and regardless of their last sorafenib dose. The sequence of sorafenib followed by regorafenib for hepatocellular carcinoma may extend survival beyond what has been previously reported. ClinicalTrials.gov NCT01774344.
RCT Entities:
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 <0.0001). This exploratory analysis describes outcomes of sequential treatment with sorafenib followed by regorafenib. 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) in RESORCE was analyzed by TTP during prior sorafenib treatment. RESULTS: HRs (regorafenib/placebo) for OS by last sorafenib dose were similar (0.67 for 800 mg/day; 0.68 for <800 mg/day). Rates of grade 3, 4, and 5 adverse events with regorafenib by last sorafenib dose (800 mg/day vs. <800 mg/day) were 52%, 11%, and 15% vs. 60%, 10%, and 12%, respectively. Median times (95% CI) from the start of sorafenib to death were 26.0 months (22.6-28.1) for regorafenib and 19.2 months (16.3-22.8) for placebo. Median time from the start of sorafenib to progression on sorafenib was 7.2 months for the regorafenib arm and 7.1 months for the placebo arm. An analysis of TTP in RESORCE in subgroups defined by TTP during prior sorafenib in quartiles (Q) showed HRs (regorafenib/placebo; 95% CI) of 0.66 (0.45-0.96; Q1); 0.26 (0.17-0.40; Q2); 0.40 (0.27-0.60; Q3); and 0.54 (0.36-0.81; Q4). CONCLUSIONS: These exploratory analyses show that regorafenib conferred a clinical benefit regardless of the last sorafenib dose or TTP on prior sorafenib. Rates of adverse events were generally similar regardless of the last sorafenib dose. LAY SUMMARY: This analysis examined characteristics and outcomes of patients with hepatocellular carcinoma who were treated with regorafenib after they had disease progression during sorafenib treatment. Regorafenib provided clinical benefit to patients regardless of the pace of their disease progression during prior sorafenib treatment and regardless of their last sorafenib dose. The sequence of sorafenib followed by regorafenib for hepatocellular carcinoma may extend survival beyond what has been previously reported. ClinicalTrials.gov NCT01774344.
Authors: Changhoon Yoo; Joong-Won Park; Yoon Jun Kim; Do Young Kim; Su Jong Yu; Tae Seop Lim; Su Jin Lee; Baek-Yeol Ryoo; Ho Yeong Lim Journal: Invest New Drugs Date: 2018-12-07 Impact factor: 3.850