Regorafenib phase III results strongly support use in GIST

Regorafenib is effective for patients with gastrointestinal stromal tumors (GISTs) who have failed to respond to treatment with imatinib and sunitinib, trial results show.

The oral multikinase inhibitor provides a new option for patients with the rare tumors, the majority of whom ultimately develop resistance to therapy, the authors report in The Lancet.

"This… phase 3 trial shows that oral regorafenib can indeed provide a significant progression-free survival benefit compared with placebo in patients with pretreated, progressive metastatic GIST," say George Demetri (Dana Farber Cancer Institute & Harvard Medical School, Boston, Massachusetts, USA) and colleagues.

The study included 132 patients randomly assigned to receive regorafenib 160 mg once daily and 66 patients who received placebo. Patients received treatment for the first 3 weeks of a 4-week cycle that were repeated until disease progression, unacceptable effects, or withdrawal from the study. The median treatment time was 22.9 weeks in the regorafenib group and 7.0 weeks in the placebo group.

Progression-free survival was almost five times greater in the regorafenib group at 4.8 months compared with 0.9 months in the placebo group. The authors note that progression-free survival was not affected by the number of previous treatments a patient had received.

The disease control rate was also significantly greater among regorafenib-treated patients at 52.6% compared with 9.1% for placebo-treated patients.

However, the authors found no significant difference in overall survival among the two groups, with the deaths of around one-fifth of patients in each group during 12 months of follow up. They say that this finding is likely due to the high crossover rate (85%) from placebo to active treatment following disease progression confounding their results.

The phase III results for regorafenib in colorectal cancer are also reported in The Lancet and were announced earlier this year (click here[o1]).

In an accompanying comment, Tom Waddell and David Cunningham, of the Royal Marsden Hospital in Sutton, UK, say that regorafenib holds greatest promise in GIST.

"In the relatively rare GIST, the case for routine use of this drug in patients who have failed imatinib and sunitinib is strong, despite the apparent absence of benefit in terms of overall survival."

However, they say that in the colorectal cancer studies, around 50% of patients progressed within 8 weeks and suffered high rates of adverse effects, and therefore molecular markers are needed to identify patients who will benefit.

The manufacturers have applied to both the US Food and Drug Administration and the European Medicines Agency for approval of regorafenib as a third-line treatment for GIST.

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