BARCELONA, Spain—Citing its results as “statistically significant and clinically meaningful,” global pharmaceutical company Bayer announced a successful Phase 3 RESORCE trial indicating Stivarga (regorafenib) tablets achieved a median overall survival improvement in patients diagnosed with unresectable hepatocellular carcinoma (HCC)—those who also progressed after treatment with Nexavar (sorafenib) tablets.
Results from the study were first presented at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer in Barcelona, Spain. Bayer plans to submit data from the RESORCE (REgorafenib after SORafenib in patients with hepatoCEllular carcinoma) study as the basis for receiving the marketing authorization of regorafenib in the treatment of unresectable HCC in the United States and other markets worldwide before the end of the year, the company reported.
“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,” states Dr. Jordi Bruix of the Hospital Clinic at University of Barcelona. “The improvement in overall survival seen with regorafenib in the RESORCE study signals the addition of a potential option in this treatment setting.”
HCC is the most common form of liver cancer, representing 70 to 85 percent of liver cancer worldwide. Liver cancer is the fifth most common cancer in men and seventh most common in women. More than 780,000 cases of liver cancer are diagnosed worldwide each year, and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer, Bayer reports.
Mark Rutstein, vice president of oncology clinical development at Bayer, states, “Bayer has a deep heritage in the exploration of therapeutic options for HCC, since the introduction of sorafenib for unresectable HCC in 2007.”
Regorafenib is a multikinase inhibitor whose mechanism of action is more commonly associated with preventing or slowing the growth of tumors, rather than reducing tumor size, Rutstein says. By preventing tumor growth, multikinase inhibitors have the potential to prolong survival.
Kinase inhibitors “are typically studied and incorporated into treatment strategies in advanced disease settings in which cure is no longer an option,” Rutstein tells DDNews. “[Kinase inhibitors] are important treatments proven to extend survival in many difficult-to-treat tumors.”
He points out that “the overall response rate is only one of several key secondary efficacy endpoints.” The results of the RESORCE trial “demonstrate consistent evidence of efficacy for the primary overall survival endpoint, as well as the key secondary efficacy endpoints.”
“We have come to understand the commonalities among various types and subtypes of cancer, along with the underlying mechanisms of cancer initiation and progression that exist when key molecular signaling proteins and pathways are mutated or activated,” Rutstein explains.
Because these processes are replicated across different areas of the body, both in normal cell growth and cancer cell growth, “we can reasonably predict where a given targeted therapy or other treatment modality may work in multiple tumor types,” he says. “This may help us to tailor medicine to patients with particular characteristics—an underlying approach to targeting the right patients with the right treatment at the right time.”
Over the past decade, “several studies have tried and failed in this area,” Rutstein says. “This is a very difficult-to-treat cancer, and having positive data on a potential second-line agent may be good news for patients and may represent a significant advance in the field.”
In Bayer’s Phase 3 trial, regorafenib treatment resulted in a 38-percent reduction in risk of death for patients with unresectable HCC who progressed after treatment with sorafenib, and the median overall survival was 10.6 months for those who received regorafenib versus 7.8 months for those in the control group. The evaluation of overall survival is often considered the most clinically meaningful efficacy assessment in oncology clinical trials, according to Rutstein.
In addition to the primary endpoint of the study, which measured improvement in overall survival compared to placebo plus best supportive care, the main secondary endpoints were also met.
The median progression-free survival was 3.1 months in patients taking regorafenib versus 1.5 months in the control group. The disease control rate was 65.2 percent in the regorafenib arm versus 36.1 percent in the control arm, while the overall response rate (complete and partial response) was 10.6 percent versus 4.1 percent, respectively.
Safety and tolerability were generally consistent with the known profile of regorafenib versus placebo, which includes cases of hypertension in patients taking regorafenib versus the control group (15.2 percent versus 4.7 percent); hand-foot skin reaction (12.6 percent versus 0.5 percent); fatigue (9.1 percent versus 4.7 percent); and diarrhea (3.2 percent versus 0 percent).
The trial researchers enrolled approximately 573 patients of all HCC histologies across 152 sites in Asia, Australia, Europe, North America and South America, who were randomized in a 2:1 ratio to receive either regorafenib plus best supportive care or placebo plus best supportive care.
