Regorafenib after sorafenib lengthens OS for advanced liver cancer

Patients with advanced liver cancer experienced clinical benefit with regorafenib after disease progression on sorafenib, according to findings published in Journal of Hepatology.

Benefits remained significant regardless of the pace of disease progression.

“Since the approval of sorafenib in 2008, one of the most important unmet needs in the treatment of hepatocellular carcinoma has been the development of agents that improve outcomes after disease progression during sorafenib treatment,” Richard S. Finn, MD, assistant professor of medicine at David Geffen School of Medicine at UCLA, and colleagues wrote. “To that end, several phase 3 trials evaluating novel drugs in this population were conducted but, until recently, all failed to meet their primary endpoint of improving OS for these patients.”

However, the phase 3 RESORCE trial found that second-line regorafenib (Stivarga, Bayer) improved OS compared with placebo among patients whose disease progressed during treatment with sorafenib.

“This improvement in OS seen with regorafenib in the second-line setting in hepatocellular carcinoma may be the beginning of incremental improvements in outcomes, similar to those observed in other advanced cancers,” Finn and colleagues wrote.

The researchers conducted an exploratory analysis of the phase 3 RESORCE trial — in which 573 patients with hepatocellular carcinoma that had progressed during therapy with sorafenib had been randomly assigned 2:1 to receive either regorafenib 160 mg daily or placebo for 3 weeks on and 1 week off — to describe outcomes of sequential treatment with sorafenib followed by regorafenib.

The study included patients from 152 centers in 21 countries. Patients were assigned to their respective groups at 2 to 10 weeks following their last dose of sorafenib, and received treatment until unacceptable toxicity, disease progression or death.

Researchers evaluated the drug’s efficacy and safety and assessed time from the start of sorafenib until death, as well as time to progression as defined by time to progression during prior sorafenib treatment.

HR for regorafenib vs. placebo group for OS appeared similar by last sorafenib dose (0.67 for 800 mg per day; 0.68 for < 800 mg per day).

When evaluated by last sorafenib dose, patients assigned regorafenib after a final sorafenib dose of 800 mg per day had similar rates of grade 3 (52% vs. 60%), grade 4 (11% vs. 10%) and grade 5 (15% vs. 12%) adverse events as those who had a final sorafenib dose of less than 800 mg per day.

The median time to death from the start of sorafenib was 26 months in the regorafenib group (95% CI, 22.6-28.1) and 19.2 months (95% CI, 16.3-22.8) in the placebo group.

The median time from the start of progression during sorafenib therapy was 7.2 months for patients assigned to regorafenib and 7.1 for placebo.

When researchers divided patients into quartiles defined by time to progression on sorafenib, the regorafenib group showed HRs of 0.66 (95% CI, 0.45-0.96) in the first quartile compared with placebo, 0.26 (95% CI, 0.17-0.4) in the second, 0.4 (95% CI, 0.27-0.6) in the third and 0.54 (95% CI, 0.36-0.81) in the fourth.

“The results presented here suggest that for certain patients with hepatocellular carcinoma who no longer benefit from resection, local ablation or chemoembolization, treatment with the sequence of sorafenib followed by regorafenib may extend survival beyond what has been previously reported,” the researchers wrote. – by Andy Polhamus

Disclosures: Finn reports consulting fees from Bayer, Bristol-Myers Squibb, Eisai, Eli Lilly, Merck, Pfizer and Roche. Please see the study for all other authors’ relevant financial disclosures.