Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study

Abstract Background The RAF–MEK–ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. Methods Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400 mg bid (arm A) or without sorafenib (arm B). Results One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7–6.5) and 4.5 months (95% CI: 2.5–5.2), respectively (HR = 0.92; 95% CI: 0.62–1.35). Median overall survival was 7.5 (95% CI: 5.6–9.7) and 8.3 months (95% CI: 6.2–8.7), respectively (HR = 0.95; 95% CI: 0.62–1.48). Response rates were 3.4% in arm A and 3.6% in arm B. Conclusions Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.