Persons with metastatic colorectal cancer or gastrointestinal stromal tumors (GISTs) may garner some survival benefit from the multikinase inhibitor regorafenib after standard treatments have failed, according to two studies from The Lancet appearing simultaneously online ahead of print.

Although several drugs are available for the treatment of metastatic colorectal cancer, the patient eventually develops resistance to all therapies, explains a statement issued by The Lancet to describe the findings of the two studies. GISTs, which are soft-tissue sarcomas, can be surgically removed in their early stages. However, more than 40% of cases recur and metastasize. Currently, imatinib and sunitinib are the only two agents approved for the treatment of GISTs.

In one study, conducted by Axel Grothey, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, persons with metastatic colorectal cancer and progression during or within 3 months after the last standard therapy were randomized to receive best supportive care plus oral regorafenib 160 mg (500 patients) or placebo (253 patients) once daily. Median overall survival was 6.4 months in the regorafenib group, compared with 5 months in the placebo group. The results showed regorafenib to be the first small-molecule multikinase inhibitor to demonstrate survival benefits in metastatic colon cancer that has progressed after all standard therapies.

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In the second trial, George D. Demetri, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, Massachusetts, and colleagues assigned 133 patients with metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib, to receive regorafenib, and 66 similar patients to receive placebo. Median progression-free survival was 4.8 months for the treatment group and 0.9 months for the placebo group.

The researchers concluded that oral regorafenib can significantly improve progression-free survival compared with placebo in persons with metastatic GIST after progression on standard treatments. To the investigators’ knowledge, this was the first clinical trial showing benefit from a kinase inhibitor in this highly refractory population of patients.

In both trials, regorafenib yielded a high rate of adverse effects, the most severe being hypertension; fatigue; diarrhea; and reddening, swelling, numbness, and peeling of the skin on the hands and feet. However, these reactions were expected based on information from earlier trials of the drug, and in most cases could be managed by reducing or interrupting the dose.