Until now, only Imatinib ( Gleevec, Glivec ) and Sunitinib ( Sutent ) have proven clinical benefit in patients with gastrointestinal stromal tumours ( GIST ), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression.
Researchers aimed to assess efficacy and safety of Regorafenib ( Stivarga ) in patients with metastatic or unresectable GIST progressing after failure of at least Imatinib and Sunitinib.
GRID is phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous Imatinib and Sunitinib were randomised in a 2:1 ratio to receive either oral Regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle.
The primary endpoint was progression-free survival ( PFS ). At disease progression, patients assigned placebo could crossover to open-label Regorafenib.
Analyses were by intention to treat.
A total of 240 patients were screened and 199 were randomised to receive Regorafenib ( n=133 ) or matching placebo ( n=66 ).
Median progression-free survival was 4.8 months for Regorafenib and 0.9 months for placebo ( hazard ratio, HR=0.27, p less than 0.0001 ).
After progression, 56 patients ( 85% ) assigned placebo crossed over to Regorafenib.
Drug-related adverse events were reported in 130 ( 98% ) patients assigned Regorafenib and 45 ( 68% ) patients assigned placebo.
The most common Regorafenib-related adverse events of grade 3 or higher were hypertension ( 23% ), hand-foot skin reaction ( 20% ), and diarrhoea ( 5% ).
The results of GRID study have shown that oral Regorafenib can provide a significant improvement in progression-free survival compared with placebo in patients with metastatic GIST after progression on standard treatments.
This is the first clinical trial to show benefit from a kinase inhibitor in this highly refractory population of patients. ( Xagena )
Demetri GD et al, Lancet 2013; 381: 295-302