Regorafenib (Stivarga) demonstrates the first survival benefit in second-line setting for patients with hepatocellular carcinoma (HCC) who have progressed on sorafenib, according to results of the phase III RESORCE trial published in <em>The Lancet</em>.
Jordi Bruix, MD
Regorafenib (Stivarga) demonstrates the first survival benefit in second-line setting for patients with hepatocellular carcinoma (HCC) who have progressed on sorafenib, according to results of the phase III RESORCE trial published inThe Lancet.1
“Regorafenib has the potential to become the new standard or care for patients with hepatocellular carcinoma who progress on sorafenib,” lead author Jordi Bruix, MD said when presenting the data at the 2016 ESMO Annual Congress.
In the RESORCE trial, the oral multikinase inhibitor demonstrated a survival benefit of 2.8 months over placebo, with a median overall survival (OS) of 10.6 months (95% CI, 9.1-12.1) with regorafenib versus 7.8 months (95% CI, 6.3-8.8) on placebo (HR, 0.63; 95% CI, 0.50-0.79; one-sidedP<.0001).
Complete responses were achieved by 2 patients on regorafenib while partial responses were noted in 38 patients (10%) for an objective response rate of 11%. Stable disease was achieved in 206 patients (54%).
Patients were admitted into the trial based on Barcelona Clinic Liver Cancer (BCLC) stage B or C, at least 1 lesion by RECIST v1.1 criteria, unresectable disease, and progression on prior sorafenib treatment. Overall, 573 patients were enrolled in the trial from 152 centers across 21 countries. The participants were randomized 2:1 to regorafenib at 160 mg or placebo.
A majority of the participants were male (88% in each arm), had an ECOG performance status of 0 (65% and 67% in regorafenib and placebo groups, respectively), extrahepatic disease (70% and 76%, respectively), and BCLC stage C (86% and 89%, respectively).
Median progression-free survival in the regorafenib arm (n = 379) was 3.1 months (95% CI, 2.8-4.2) versus 1.5 months (95% CI, 1.4-1.6) on placebo (n = 194). The authors noted that both the progression-free and overall survival benefits were maintained in all subgroup analyses.
Eighty-three percent of the patients receiving regorafenib and 95% of the patients on placebo discontinued treatment, most often due to disease progression. The median duration of treatment on regorafenib was 3.6 months (range, 1.6-7.6) and 1.9 months (range, 1.4-3.9) on placebo.
All patients in the regorafenib arm experienced a treatment-emergent adverse event (AE). The most common grade 3/4 AEs included hypertension (15% vs 5% in regorafenib and placebo groups, respectively), hand-foot skin reaction (13% vs 1%, respectively), fatigue (9% vs 5%, respectively), and diarrhea (3% vs 0, respectively). AEs experienced by patients on regorafenib were similar to those experienced on sorafenib.
Serious AEs occurred in 166 patients (44%) in the regorafenib group, with 10% attributed to the study drug, and in 90 patients (47%) on placebo. Seven treatment-related deaths occurred in the regorafenib arm and 2 in the placebo arm.
In the report, the authors noted that this is the first systemic therapy to show a survival benefit in patients with HCC after treatment with sorafenib, which was echoed in an editorial by Jean-Charles Nault, MD, of the Génomique fonctionnelle des Tumeurs solides in Paris, France.
“It is clear that regorafenib will become the standard of care as a second-line treatment following sorafenib failure in patients with advanced HCC,” Nault stated in his editorial.
A supplemental new drug application for regorafenib as a second-line treatment for patients with unresectable HCC was submitted to the FDA in November based on the findings from the RESORCE trial.