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Stivarga improves OS for unresectable HCC

Stivarga was safe and improved overall survival for patients with unresectable hepatocellular carcinoma, according to data from the RESORCE clinical trial recently published in The Lancet.

“The global incidence of liver cancer continues to increase and has more than tripled in the United States over the last three decades, and currently there are no proven or approved systemic second-line treatment options for patients with advanced HCC,” Jordi Bruix, MD, head of the Barcelona Liver Clinic Group, Hospital Clinic, University of Barcelona, Spain, and trial investigator, said in a press release. “The improvement in overall survival seen with [Stivarga] in the RESORCE study signals the addition of a potential option in this treatment setting.”

Jordi Bruix

Bruix and colleagues randomly assigned 573 patients with unresectable HCC whose disease progressed after treatment with Nexavar (sorafenib, Bayer HealthCare) to treatment with either 160 mg of Stivarga (regorafenib, Bayer; n = 379) for 3 weeks on and 1 week off, or placebo (n = 194) with 28 days constituting one full treatment cycle.

Results showed patients treated with regorafenib had a longer median overall survival (OS) of 10.6 months compared with 7.8 months for patients treated with placebo plus best supportive care (HR = 0.62; 95% CI, 0.5-0.78). The median progression-free survival was 3.1 months in the regorafenib-treated group compared with 1.5 months in the control group (HR = 0.46; 95% CI, 0.37‒0.56).

Disease control rate defined by mRECIST criteria was 65.2% in regorafenib-treated patients compared with the placebo group (36.1%; P < .001). The overall response rate (complete and partial) was 10.6% vs. 4.1% (P = .005).

More patients in the regorafenib-treated group experienced grade 3 adverse events (79.7%) compared with placebo (58.5%). Common grade 3 adverse events included hypertension, hand-foot skin reaction, fatigue and diarrhea. Approximately 68% of patients treated with regorafenib underwent dose modification due to adverse events compared with 31.1% of patients treated with placebo.

Patients treated with placebo had a higher mortality rate compared with regorafenib-treated patients after 30 days post-treatment (19.7% vs. 13.4%).

Bayer submitted data from the RESORCE study for marketing authorization of regorafenib for the treatment of unresectable HCC in the U.S. and worldwide in November 2016.

The researchers concluded: “Regorafenib significantly improved OS in patients with HCC who progressed during treatment with sorafenib. Adverse events were consistent with the known safety profile of regorafenib.”

“This study represents a breakthrough in the management of hepatocellular carcinoma, since it provides evidence for clinical benefits in an area that was an unmet medical need,” Josep M. Llovet, MD, founder and director of the Liver Cancer Program and professor of medicine and Liver Diseases at the Icahn School of Medicine at Mount Sinai, said in a press release. “Regorafenib has shown it can improve survival in patients with advanced hepatocellular carcinoma progressing on sorafenib. Previously, no treatment was available for these patients.”

In light of these results, “it is clear that regorafenib will become the standard of care as a second-line treatment following sorafenib failure in patients with advanced HCC,” Jean-Charles Nault, MD, PhD, of the French Institute of Health and Medical Research, wrote in a related editorial. However, “the main area of uncertainty lies in the tolerance and efficacy of regorafenib in patients not tolerating sorafenib,” he noted. “Further data are warranted in this subpopulation of patients.” – by Melinda Stevens and Adam Leitenberger

Reference:

Bruix J, et al. Abstract #LBA-03. Presented at: European Society of Medical Oncology World Congress on Gastrointestinal Cancer; June 29-July 2, 2016; Barcelona, Spain.

Disclosure: This study was funded by Bayer. Bruix reports consulting for AbbVie, Arqule, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, BTG, Gilead Sciences, Kowa, Novartis, Onxeo, OSI, Roche and Terumo. Nault reports no relevant financial disclosures.

Editor's note: These data were originally presented at the European Society of Medical Oncology 18th World Congress on Gastrointestinal Cancer. This article was updated on January 23 with additional information after publication in The Lancet.