In the Pipeline

SAN FRANCISCO – Adding the oral, investigational multikinase inhibitor regorafenib to best supportive care for metastatic colorectal cancer resulted in a modest but statistically significant increase in median overall survival in the phase III CORRECT trial.

The 760-patient study was stopped early, so that patients in a control group could receive the study drug, researchers reported at the Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Dr. Axel Grothey

Regorafenib added a median benefit of just 1.4 months, compared with placebo and best supportive care (6.4 months vs. 5.0 months; hazard ratio, 0.77; P = .0052), lead investigator Dr. Axel Grothey said. Though the time was short, he noted, all participants were running out of options, after the failure of standard therapies, including bevacizumab (Avastin) and epidermal growth factor receptor (EGFR) inhibitors in those who had KRAS wild-type tumors.

Regorafenib "identifies itself as a potential new standard of care in this patient population," and will move into earlier lines of therapy, said Dr. Grothey, professor of oncology at the Mayo Clinic in Rochester, Minn. Phase II studies are underway to evaluate the novel Bayer drug in combination with standard chemotherapy backbones such as 5-fluorouracil and irinotecan (Camptosar).

Discussant Dr. Herbert Hurwitz of the Duke Cancer Institute in Durham, N.C., said there is good reason to question why regorafenib worked in CORRECT, as the phase I data leading up to the trial were "relatively modest," and there was no phase II trial. "Rushing from phase I to phase III can work, but I would be cautious not to overinterpret the success of the regorafenib study, particularly when looking at the novel therapeutic classes," he advised.

Dr. Herbert Hurwitz

To be eligible for the international CORRECT trial, patients had to have had progression while on or within 3 months after last receipt of approved standard therapies, which had to include a fluoropyrimidine, oxaliplatin (Eloxatin), irinotecan, bevacizumab, and, if they had KRAS wild-type disease, cetuximab (Erbitux) or panitumumab (Vectibix).

The patients had a median age of 61 years. A total of 60% had received four or more lines of prior therapy. Fifty-seven percent had tumors with a KRAS mutation.

The response rate was similar between regorafenib and placebo (1.0% vs. 0.4%), but regorafenib distinguished itself with a much higher disease-control rate than did placebo (45% vs. 15%). "So the strength of this drug is more in delaying tumor progression than inducing responses," Dr. Grothey said.

The median difference in progression-free survival (PFS) was again small, at just 0.2 months, but this corresponded to a 51% reduction in the risk of progression events (HR, 0.49; P less than .000001), he noted.

The progression-free survival curve "clearly identifies that the median difference in PFS does not fully reflect the efficacy of this drug in this patient population. These curves run together for about 50% of patients but then spread out wide. ... Clearly, the median does not reflect what’s happening," he elaborated.

01/30/12  

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FROM A SYMPOSIUM ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY

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Vitals

Major Finding: Regorafenib improved overall survival (6.4 vs. 5.0 months), progression-free survival (1.9 vs. 1.7 months), and the disease control rate (45% vs. 15%).

Data Source: A phase III randomized, double-blind trial comparing best supportive care plus either regorafenib or placebo in 760 patients with progressive metastatic colorectal cancer (the CORRECT trial)

Disclosures: Dr. Grothey reported that he is a consultant to Bayer. Dr. Hurwitz reported that he is a consultant to Bristol-Myers Squibb and Genentech/Roche; receives honoraria from Roche; and receives research funding from a dozen companies.