Results of an international Phase III trial demonstrate that the new targeted oral drug, regorafenib, can improve outcomes for patients with gastrointestinal stromal tumours (GIST) that progress due to resistance to other available treatment options, including imatinib and sunitinib.

The researchers found that progression-free survival was four times longer among patients receiving regorafenib than among those receiving placebo; all patients also received best supportive care to alleviate the symptoms of their disease.

“If approved, regroafenib will fulfill an urgent unmet need for patients with GIST who have exhausted all other treatment options,” said George Demetri, MD, Director of the Ludwig Center and Sarcoma Center at Dana-Farber Cancer Institute and Harvard Medical School in Boston.

“Targeted therapy has revolutionised treatment for this rare cancer, but we’ve been on the hunt for additional effective treatments for the 85 percent of patients whose cancer eventually develops resistance to the only two available therapies. Regorafenib appears to target GIST tumours in a different and possibly more powerful way than the current FDA-approved therapies, making it a potentially significant new option to help patients.”

Like other approved “smart drugs” for GIST, regorafenib targets abnormalities in cancer cell signaling pathways driven by an enzyme called KIT. Although initially suppressed by targeted therapies such as Gleevec, new mutations eventually evolve which lead to drug-resistant forms of the KIT enzyme, allowing the cancer to grow despite continuing the drugs which initially worked.

Regorafenib appears to inhibit the cancer-promoting signals in a unique way, working even in patients whose cancers have developed resistance to the other treatments.

In this study, researchers randomised 199 patients with metastatic and/or inoperable GIST patients to either regorafenib or placebo plus best supportive care. All had undergone prior treatment with at least standard imatinib and sunitinib therapy. Progression-free survival was significantly longer among patients treated with regorafenib, compared with placebo (0.9 months). If the disease worsened, patients on placebo were allowed switch to regorafenib treatment; in all, 85 percent of patients were able to cross over to receive regorafenib.

Because of this trial design, there was no statistical difference in overall survival between the two arms, although a non-significant trend was noted in favor of patients who started regorafenib earlier in the course of care. The drug was well-tolerated overall, with side effects similar to other approved targeted agents for GIST. 

Source: ASCO