LBA28 - Efficacy, safety, and health-related quality of life (HRQoL) of regorafenib in patients with hepatocellular carcinoma (HCC) progressing on sorafeni...

Date 08 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, non-colorectal
Topics Hepatobiliary Cancers
Presenter Jordi Bruix
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors J. Bruix1, P. Merle2, A. Granito3, Y. Huang4, G. Bodoky5, O. Yokosuka6, O. Rosmorduc7, V. Breder8, R. Gerolami9, G. Masi10, P.J. Ross11, S. Qin12, T. Song13, J. Bronowicki14, I. Ollivier-Hourmand15, M. Kudo16, M. Leberre17, A. Baumhauer18, G. Meinhardt19, G. Han20
  • 1Bclc Group, Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, CIBEREHD, 08036 - Barcelona/ES
  • 2Hepatology Unit, Groupement Hospitalier Lyon Nord, Lyon/FR
  • 3Department Of Medical And Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna/IT
  • 4Division Of Gastroenterology And Hepatology, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming University, Taipei/TW
  • 5Medical Oncology, St. Laszlo Teaching Hospital, Budapest/HU
  • 6Department Of Gastroenterology And Nephrology, Chiba University, 2608670 - Chiba/JP
  • 7Department Of Hepatology, Hôpital De La Pitié-salpétrière, Assistance Publique-Hôpitaux de Paris and Université Pierre et Marie Curie, Sorbonne Universités, Paris/FR
  • 8Department Of Clinical Biotechnologies, n.a.N. Blokhin Russian Research Center, Moscow/RU
  • 9Chu Timone, Université de la Méditerranée, Marseille/FR
  • 10Unit Of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa/IT
  • 11Department Of Medical Oncology, King's College Hospital NHS Foundation Trust, London/GB
  • 12Chinese People’s Liberation Army Cancer Center, Nanjing Bayi Hospital, 210002 - Nanjing/CN
  • 13Department Of Hepatobiliary Tumors, Tianjin Medical University Cancer Hospital, Tianjin/CN
  • 14Inserm 954, Chu De Nancy, Université de Lorraine, Nancy/FR
  • 15Service D’hépatogastroentérologie, CHU, Caen/FR
  • 16Faculty Of Medicine, Kindai University, Osaka/JP
  • 17Medical Affairs, Bayer HealthCare SAS, Loos/FR
  • 18Bayer Pharmaceuticals, Bayer Vital GmbH, 51366 - Leverkusen/DE
  • 19Clinical Development Oncology, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 20Xijing Hospital Of Digestive Diseases, The First Affiliated Hospital of the Fourth Military Medical University, Xi'an/CN



There are no proven or approved second-line systemic treatment options for HCC. We evaluated regorafenib, an oral multikinase inhibitor, in patients with HCC who had disease progression on sorafenib.


Adults with BCLC stage B or C HCC who had radiological progression on sorafenib, Child-Pugh A liver function, and ECOG PS 0–1 were randomized 2:1 to regorafenib 160 mg/day or placebo on weeks 1–3 of each 4-week cycle until progression, death, or unacceptable toxicity. The primary endpoint was overall survival (OS). HRQoL was assessed by the FACT-Hep and EQ-5D questionnaires.


A total of 573 patients were randomized (regorafenib 379; placebo 194) and baseline characteristics were balanced. The regorafenib group had a 37% reduction in the risk of death (HR 0.63; 95%CI 0.50–0.79; p < 0.001); median OS (regorafenib vs placebo) was 10.6 vs 7.8 months. Regorafenib improved progression-free survival (HR 0.46; 95%CI 0.37–0.56; p < 0.001), time to progression (HR 0.44; 95%CI 0.36–0.55; p < 0.001), and the disease control rate (65.2% vs 36.1%; p < 0.001). Rates of grade ≥3 adverse events were 79.7% with regorafenib and 58.5% with placebo. Most common grade ≥3 adverse events occurring more frequently with regorafenib included hypertension (15.2% vs 4.7%), hand–foot skin reaction (12.6% vs 0.5%), fatigue (9.1% vs 4.7%), and diarrhea (3.2% vs 0%). The EQ-5D index, EQ-5D VAS, and FACT-G scores were similar in the treatment groups (Table). Although the FACT-Hep total score favored placebo, the difference did not meet the established minimally important threshold of 8–9 points.

Least square mean (LSM) time-adjusted AUC (95% CI) Regorafenib Placebo P-value
EQ-5D index 0.76 (0.75–0.78) 0.77 (0.75–0.79) 0.47
EQ-5D visual analogue scale (VAS) 71.68 (70.46–72.90) 73.45 (71.84–75.06) 0.06
Functional Assessment of Cancer Therapy-General (FACT-G) 75.14 (74.12–76.16) 76.55 (75.20–77.90) 0.07
FACT-Hep total 129.31 (127.84–130.79) 133.17 (131.21–135.12)


Regorafenib significantly improved OS in patients with HCC who progressed during sorafenib treatment. Adverse events were consistent with the known safety profile of regorafenib with no clinically meaningful differences in HRQoL between groups.

Clinical trial identification ID: NCT01774344

Legal entity responsible for the study





J. Bruix: Advisory board membership: Bayer, BMS, Arqule, Roche, Gilead, AbbVie, Terumo, BTG, Kowa, Glaxo, Novartis Corporate-sponsored research: Bayer. G. Bodoky: I am advisory board member of: Novartis, Bayer, Roche, Janssen, Pfizer. O. Rosmorduc: One-time fee or honoraria from Bayer, Sirtex, Ipsen and BMS. V. Breder: Honoraria for lectures - Roche, Boeringher, Lilly, Astra Zeneca, BMS, MSD, Novartis. R. Gerolami: Member of an advisory board for Bayer. P.J. Ross: Advisory Boards: Bayer, Celgene, Baxalta (now Shire), BMS, Amgen Travel/meeting attendance support: Bayer, Amgen, Celgene, Merck Serono Speakers Bureau: Merck Serono, Celgene, Roche, Sirtex Grant funding for Research: Sanofi. J-P. Bronowicki: Membership on an advisory board: yes, Bayer Corporate; sponsored research: yes Grant to my institution for phase II or III studies: Bayer. I. Ollivier-Hourmand: I disclose financial support from Bayer for a medical congress but no other conflict or interest in relation with this work. M. Kudo: Lecture: Bayer, Kowa, Taiho Grant: Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Eisai. M-A. Leberre, A. Baumhauer, G. Meinhardt: Employee of Bayer. All other authors have declared no conflicts of interest.