Investigational drug improves colorectal cancer survival
MedWire News: The investigational multikinase inhibitor regorafenib significantly prolongs survival among patients with metastatic colorectal cancer (mCRC) who have exhausted all other standard therapy options, show results of a phase III, randomized, placebo-controlled trial.
"For years, patients with metastatic colorectal cancer have faced a devastating impasse when standard chemotherapies have failed to halt the growth of tumors and physicians have run out of effective drugs to offer them," said Axel Grothey (Mayo Clinic, Rochester Minnesota, USA) at the 2012 Gastrointestinal Cancers Symposium, in San Francisco, California, USA.
"This is the first novel agent in 8 years to show improvement in overall survival of colon cancer patients who have run out of treatment options," he added.
Grothey explained that regorafenib inhibits a broad range of angiogenic, oncogenic, and stromal kinases, and therefore slows cell proliferation and blood vessel growth.
The efficacy and safety of the drug, which does not currently have approval for use in mCRC patients, was evaluated in the international phase III Patients with metastatic COloRectal cancer treated with REgorafenib or plaCebo after failure of standard Therapy (CORRECT) trial.
From May 2010 to March 2011, 760 patients with mCRC, who had progressed after all approved standard therapies, were randomly assigned to receive oral regorafenib (160 mg once daily, 3 weeks on/1 week off) plus best supportive care (n=505), or placebo plus best supportive care (n=255).
Patients continued on treatment until disease progression, death, or unacceptable toxicity.
Grothey reported that preliminary results from a preplanned interim analysis show that regorafenib reduced the risk for death by 23%, compared with placebo, during the study period.
Moreover, median overall survival - the primary study endpoint - was significantly longer in the regorafenib group than in the placebo group, at 6.5 versus 5.0 months.
Progression-free survival was also significantly longer with regorafenib than with placebo, at 1.9 versus 1.7 months, and the risk for disease progression was 51% lower in the regorafenib group during the study.
The most frequent grade 3+ adverse events observed in the regorafenib arm were hand-foot skin reaction (17%), fatigue (15%), diarrhea (8%), hyperbilirubinemia (8%), and hypertension (7%). These were not "new or unexpected," said Grothey.
Importantly, he noted that following these results, the Data Monitoring Committee recommended that the study be unblinded. Patients in the placebo arm were then offered treatment with regorafenib.
Grothey concluded that regorafenib "is the first and only agent… that has demonstrated statistically significant overall survival benefit" in patients with metastatic colorectal cancer who have failed all approved standard therapies."
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By Laura Cowen