Patients with metastatic gastrointestinal stromal tumor (GIST) with primary KIT exon 11 mutations, as well as those with succinate dehydrogenase (SDH)-deficient tumors, may benefit from treatment with regorafenib, long-term data from the phase 2 GRID trial suggest.1

The GRID trial was the basis for regulatory approval of regorafenib as third-line therapy for patients with metastatic and/or unresectable GIST. Adult patients who experienced failure with at least imatinib and sunitinib received regorafenib 160 mg orally daily for 21 days of each 28-day cycle.

In this analysis of 31 patients who had received at least 1 dose of regorafenib, the clinical benefit rate was 76% (95% CI, 58-89), including 6 partial responses, during a median follow-up of 41 months.

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Median progression-free survival was 13.2 months (95% CI, 9.2-18.3), and 4 patients remained free of disease progression at the time of study closure; each achieved clinical benefit for more than 3 years. Median overall survival was 25 months (95% CI, 13.2-39.1).

Subgroup analyses demonstrated that patients who harbored a KIT exon 11 mutation achieved the longest median progression-free survival of 13.4 months, while patients with KIT/PDGFRA wild-type, non-SDH-deficient tumors experienced a median progression-free survival of 1.6 months (P < .0001). Patients with SDH-deficient tumors achieved durable objective responses.

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The long-term toxicity profile was consistent with previously reported data. Dose adjustments were required to manage treatment-related adverse events, the most common of which were hand-foot skin reaction and hypertension.                      


  1. Ben-Ami E, Barysauskas CM, von Mehren M, et al. Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol. doi: 10.1093/annonc/mdw228 [Epub ahead of print]