Grant McArthur, MB, BS, PhD, Head of the Cancer Therapeutics Program at the Peter MacCallum Cancer Centre in Melbourne, Australia, congratulated the investigators on a rapidly accrued, well-conducted, and ethical study that encouraged crossover to the active arm.

He noted that regorafenib is an “extremely interesting” inhibitor of a broad range of KIT mutants, showing impressive activity across all gastrointestinal stromal tumor (GIST) genotypes. Regorafenib can also inhibit other kinases that may be relevant in the GIST cells themselves and in the microenvironment, “which may be why we are seeing third-line activity,” he proposed.

“This was a randomized study against a standard of care,” Dr. McArthur noted, suggesting that it may have been more informative to compare regorafenib to an active treatment, as was done in a recent German trial of third-line nilotinib (Tasigna).¹ In the control arm of that study, patients could receive (continue on, or switch to) sunitinib (Sutent) or imatinib (Gleevec), or could receive placebo. Median progression-free survival was 3.7 months for nilotinib (similar to the control arms), whereas it was 4.8 months with regorafenib in the GRID trial. 

“We must be cautious comparing different studies, but this gets to the point of whether placebo was the best control arm for the study,” Dr. McArthur said. “Clearly this is a positive study, and no doubt regorafenib is a viable third-line option. However, best supportive care as the comparator is one previous standard of care; the alternative is continuation of KIT inhibitors at progression, and that may have been an alternative comparator for this study.” ■

Disclosure: Dr. McArthur reported no potential conflicts of interest.

Reference

1. Reichardt P, Blay JY, Gelderblom H, et al: Phase III study of nilotinib versus beset supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. Ann Oncol. February 21, 2012 (early release online).