Abstract 3822
Background
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.
Methods
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.
Results
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) | ConclusionsRegorafenib 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 identificationClinicaltrials.gov ID: NCT01774344 Legal entity responsible for the studyBayer FundingBayer DisclosureJ. 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. Resources from the same session2637 - Randomized, open-label, phase III study comparing irinotecan plus S-1 with S-1 alone in patients with advanced esophageal squamous cell carcinoma after failure of prior platinum- or taxane-based chemotherapy: Results of an interim analysisPresenter: Jing Huang Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 2321 - Randomized phase II study of S-1 and concurrent radiotherapy with versus without induction chemotherapy of gemcitabine for locally advanced pancreatic cancer (LAPC): Final analysis of JCOG1106Presenter: Tatsuya Ioka Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 1861 - Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Prognosis, efficacy, and safety by liver disease etiologyPresenter: Takuji Okusaka Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 2268 - Prognostic factors in curative treatment of gallbladder cancer - Data of 950 cases of “The German- Registry”Presenter: Thorsten Goetze Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 2823 - Phase III study comparing intraperitoneal paclitaxel plus S-1/paclitaxel with S-1/cisplatin in gastric cancer patients with peritoneal metastasis: PHOENIX-GC trialPresenter: Yoshiyuki Fujiwara Session: Gastrointestinal tumours, non-colorectal Resources: Abstract 4066 - Molecular characteristics of hepatocellular carcinomas (HCC) from different age groupsPresenter: Celina Ang Session: Gastrointestinal tumours, non-colorectal Resources: Abstract Invited discussant abstracts LBA26, LBA27 and 616PDPresenter: Eric Van Cutsem Session: Gastrointestinal tumours, non-colorectal Resources: Slides Invited discussant abstracts 620PD, 621PD and 622PDPresenter: Eduardo Diaz Rubio Session: Gastrointestinal tumours, non-colorectal Resources: Slides Invited discussant abstracts 617PD, 618PD, 619PD and LBA28Presenter: Florian Lordick Session: Gastrointestinal tumours, non-colorectal Resources: Slides 3707 - Final results of NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapyPresenter: Li-Tzong Chen Session: Gastrointestinal tumours, non-colorectal Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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