The multikinase inhibitor regorafenib (Stivarga) prolonged progression-free survival vs placebo in patients with previously treated advanced gastric carcinoma, in a phase II trial reported in the Journal of Clinical Oncology by Nick Pavlakis, MBBS, PhD, of the University of Sydney, Australia, and colleagues. A regional difference in treatment effect was observed.
In the double-blind trial, 147 evaluable patients with 1 or 2 lines of prior chemotherapy for advanced disease from sites in Canada, Australia, New Zealand, and South Korea were randomized 2:1 between November 2012 and February 2014 to receive best supportive care plus oral regorafenib at 160 mg (n = 97) or placebo on days 1 to 21 of 28-day cycles. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival.
Patients had a median age of 62 to 63 years; 80% in both groups were male; 42% and 58% in both groups had received 1 and 2 prior lines of therapy, respectively; 37% of patients were from South Korea, 52% were from Australia or New Zealand, and 11% were from Canada.
Median progression-free survival was 2.6 months (95% confidence interval [CI] = 1.8–3.1 months) in the regorafenib group vs 0.9 months (95% CI = 0.9–0.9 months) in the placebo group (hazard ratio [HR] = 0.40, P < .001). The treatment effect was greater among patients from South Korea (HR = 0.12, P < .001) than from Australia, New Zealand, and Canada combined (HR = 0.61, P = .03; P < .001 for interaction); otherwise, the treatment effect was consistent across age, neutrophil-to-lymphocyte ratio, primary disease site, lines of chemotherapy, presence of peritoneal metastasis, number of metastatic sites, and plasma vascular endothelial growth factor A levels.
Median overall survival was 5.8 vs 4.5 months (HR = 0.74, P = .147). After disease progression, 29 placebo patients received regorafenib.
Grade ≥ 3 adverse events occurred in 67% vs 52% of patients, with the most common events in the regorafenib group being hypertension (10% vs 2%), increased aspartate transaminase (9% vs 0%), and increased alanine transaminase (8% vs 6%). Serious adverse events occurred in 32% vs 18%, with the most common events being gastrointestinal disorders (11% vs 0%) and infection (6% vs 2%).
The investigators concluded: “In this phase II trial, regorafenib was effective in prolonging [progression-free survival] in refractory advanced gastric adenocarcinoma. A phase III trial is planned.”
The study was supported by Bayer HealthCare Pharmaceuticals and the Australian National Health and Medical Research Council. ■