Chicago, IL—Regorafenib, the orally administered investigational tyrosine kinase inhibitor (TKI) that has shown activity in metastatic chemorefractory colorectal cancer, dramatically delayed disease progression in patients with a treatment-refractory metastatic gastrointestinal stromal tumor (GIST) in GRID, a phase 3 clinical trial, said lead investigator George D. Demetri, MD, Associate Professor, Department of Medicine, Harvard Medical School, and Director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, at ASCO 2012.
The median progression-free survival (PFS) reached 4.8 months with regorafenib compared with only 0.9 months in the placebo arm, for a 73% reduction in risk (P <.001). The disease control rate at 12 months was 52.6% with regorafenib and 9.1% with placebo.
“There was a significant robust effect, regardless of the number of prior inhibitors that these patients had been exposed to. Regorafenib has the potential to fulfill an unmet need for GIST patients progressing after imatinib and sunitinib, and potentially represents a new standard of care,” Dr Demetri said.
GIST is the most common subtype of sarcoma, and until the marketing of imatinib and then sunitinib, this condition was essentially untreatable. The TKIs changed the typical course of this disease, with prognosis ranging from ≤6 months, survival to ≥5 years.
However, the tumors almost universally eventually become resistant to these 2 approved TKIs, Dr Demetri said.
GRID was an international, randomized, placebo-controlled trial that quickly accrued 236 patients with metastatic, unresectable GIST who were intolerant of imatinib and sunitinib, or whose disease progressed despite treatment with these agents. The patients were assigned to daily regorafenib or to placebo plus best supportive care; 74% of the patients had received 2 previous lines of therapy and 59% had received >2 lines.
Despite the significant difference in PFS between the 2 arms, the overall survival rate was similar, presumably because 85% of the placebo-recipient patients crossed over to receive regorafenib upon disease progression. Median survival has not yet been reached in either arm.
Treatment-related adverse events were similar to what is typically seen with multitargeting TKIs.
Grant McArthur, PhD, of the Peter MacCallum Cancer Centre, East Melbourne, Australia, commented on the study, saying, “Clearly, this is a positive study, and there is no doubt that regorafenib is a viable third-line treatment option now for our patients.”—CH