Regorafenib Improves Survival in Phase III HCC Study

The manufacturer of the multikinase inhibitor, Bayer, announced the topline OS findings along with a noticed that the safety profile for the TKI was comparable to previously reported outcomes. Bayer plans to present the full results from the trial at an upcoming scientific meeting.

“Effective treatment options are urgently needed for patients with liver cancer,” Joerg Moeller, MD, member of the Executive Committee of Bayer AG's Pharmaceutical Division and head of development, said in a statement. “With sorafenib having been a major advance in the treatment of unresectable HCC, regorafenib could now become the second proven systemic option for the treatment of liver cancer.”

The multicenter, double-blind, placebo-controlled phase III RESORCE trial included 573 patients with HCC who progressed on sorafenib, which is the standard frontline therapy. Patients had an ECOG performance status of 0 or 1 and could not have received prior systemic treatments for HCC other than sorafenib.

The trial randomized patients in a 2:1 ratio to regorafenib plus best supportive care or placebo plus best supportive care. Patients received 160 mg of regorafenib once daily or placebo for 3 weeks followed by 1 week off, with 1 complete treatment cycle comprising 28 days.

OS was the primary outcome measure of the study. Secondary endpoints included progression-free survival, time to progression, objective response rate, and disease control rate. Safety and tolerability were also assessed throughout the study.

Previously published phase II data for regorafenib demonstrated antitumor activity with acceptable toxicity in patients with intermediate or advanced HCC who had progressed following first-line sorafenib. This open-label, single-arm study included 36 patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function (Child-Pugh class A).

In the phase II study, patients received regorafenib (160 mg once daily, 3 weeks on/1 week off) until disease progression or unacceptable toxicity. The primary outcome measure was safety, with secondary efficacy endpoints that included overall survival and time to progression.

After median treatment duration of 19.5 weeks (range, 2-103), disease control was achieved in 26 patients, including 1 patient with a partial response and 25 patients with stable disease. The median OS was 13.8 months and the median time to progression was 4.3 months.

Three patients were still receiving treatment at the time of the data cutoff. Patient discontinuations were due to adverse events (AEs; n = 20), disease progression (n = 10), consent withdrawal (n = 2), and death (n = 1). Dose reductions were required for 17 patients, mostly due to AEs (n = 15). Treatment interruptions occurred with 35 patients due to AEs (n = 32) or patient error (n = 11).

The most common treatment-related all-grade AEs were hand-foot skin reaction (n = 19), diarrhea (n = 19), fatigue (n = 19), hypothyroidism (n = 15), anorexia (n = 13), hypertension (n = 13), nausea (n = 12) and voice changes (n = 10). Grade ≥3 AEs occurring most frequently included hand-foot skin reaction (n = 5), diarrhea (n = 2), fatigue (n = 6), and hypertension (n = 1).

The oral multikinase inhibitor regorafenib inhibits VEGFR 1-3, as well as TIE-2, RAF-1, BRAF, BRAFV600, KIT, RET, PDGFR, and FGFR. The drug currently has approved indications from the FDA for the treatment of patients with metastatic colorectal cancer and advanced gastrointestinal stromal tumors.

Bruix J, Tak WY, Gasbarrini A, et al. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study.Eur J Cancer. 2013;49(16):3412-3419.