Study Finds Regorafenib Increases Progression-Free Survival in Advanced Gastric Cancer

Key Points

  • Regorafenib significantly prolonged progression-free survival in patients with previously treated advanced gastric carcinoma.
  • The treatment effect was greater in South Korea than in other regions.
  • A phase III trial of regorafenib in this patient population is planned.

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 Pavlakis et al. A regional difference in treatment effect was observed.

Study Details

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, and 42% and 58% in both groups had received 1 and 2 prior lines of therapy; 37% of patients were from South Korea, 52% were from Australia or New Zealand, and 11% were from Canada.

Progression-Free Survival

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.

Adverse Events

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. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned.”

The study was supported by Bayer HealthCare Pharmaceuticals and the Australian National Health and Medical Research Council.

Nick Pavlakis, MBBS, PhD, of the University of Sydney, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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