Jordi Bruix, MD
Regorafenib improved overall survival (OS), the trial’s primary endpoint, by nearly 3 months over placebo and demonstrated improved progression-free survival (PFS) and time to progression (TTP), according to Jordi Bruix, MD, of the Liver Unit Hospital Clinic, University of Barcelona, Spain, presenting them at the recent ESMO 2016 Cancer Conference in Copenhagen.
Median OS was 10.6 months with regorafenib versus 7.8 months with placebo. Regorafenib patients had a 37% reduction in the risk of death and a 54% reduction in the risk of progression compared with placebo.
Significantly prolonged median PFS of 3.1 months was observed in patients treated with regorafenib compared with 1.5 months in patients receiving placebo, (HR, 0.46; P <.001). Similarly, median TTP was 3.2 and 1.5 months, respectively, (HR, 0.44; P <.001).
"We had a higher response rate and we doubled the disease control rate in late stage hepatocellular carcinoma, a difficult cancer to treat," Bruix explained. “Regorafenib has the potential to become the new standard or care for patients with hepatocellular carcinoma who progress on sorafenib.”
Patients receiving regorafenib demonstrated a higher disease control rate of 65.2% compared with 36.1% with placebo (P <.001), and 10.6% of patients receiving regorafenib showed either complete or partial response versus 4.1% of placebo patients (P = .01).
Bruix and colleagues enrolled 573 patients from centers in 21 countries who were stratified by geographic location of Asia or non-Asia, the presence/absence of microvascular invasion or extrahepatic disease, Eastern Cooperative Oncology Group performance of 0 versus 1, and alpha-fetoprotein less than 400 ng/mL versus 400 ng/mL or greater. All patients had Barcelona Clinic Liver Cancer (BCLC) stage B or C designated HCC plus documented radiologic progression after a minimum of 20 days of sorafenib at 400 mg or more per day.
Baseline characteristics were balanced between the regorafenib and placebo arms. The patients’ median age was 63 years, 88% were male, and 87% of patients had BCLC stage C disease.
The patients were randomized 2:1 to oral regorafenib at 160 mg or placebo once daily for 1 to 3 weeks of a 4-week cycle. The median treatment duration was 3.6 (range: 0.03 to 29) months for regorafenib versus 1.9 (range: 0.2 to 27) months for placebo.
Treatment-emergent adverse events (TEAEs) leading to treatment interruption occurred in 58% of patients in the regorafenib arm versus 29% of patients on placebo. Drug-related TEAEs leading to treatment interruption occurred in 42% versus 8% of patients in the respective arms.
The most commonly reported grade adverse events ≥3 were hypertension (15.2% vs 4.7%), hand/foot skin reactions (12.8% vs 0.5%), fatigue (9.1% vs 4.7%), and diarrhea (3.2% vs 0.0%) with regorafenib versus placebo, respectively.
Bruix also reported on quality-of-life data that was collected using the EQ-50 index, EQ-50 VAS, Fact-G, FACT-Hep total, and Trial Outcome scales. Significant differences among patients receiving regorafenib and placebo were seen only on the last 2 scales; the difference between the groups was -8.85 on the FACT-Hep total, and -4.05 on the Trial Outcome Index (both P <.001).
Session co-chair Florian Lordick, MD, PhD, of the University Cancer Center in Leipzig, Germany, discussed whether regorafenib would become the new standard of care and summarized: “Maybe, yes, because regorafenib significantly improved overall survival over placebo, but there are no clinically meaningful differences in patient-reported outcomes, and there was a high rate of treatment interruption due to adverse events, suggesting that regorafenib was not well-tolerated.”
Bruix responded to this comment by pointing out that regorafenib actually was well tolerated in this cohort: “Nearly 50% of patients received the full dose and the tolerance was similar to the tolerance reported in patients with GIST [gastrointestinal stromal tumor].”
Regorafenib received FDA approval in 2013 for treatment of patients with advanced GIST who are not candidates for surgery and do not respond to imatinib and sunitinib.
Bruix, J. Efficacy, safety, and health-related quality of life (HRQoL) of regorafenib in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: Results of the international, double-blind phase 3 RESORCE trial. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. LBA28.