Phase II clinical trial of gemcitabine plus oxaliplatin in patients with metastatic pancreatic adenocarcinoma with a family history of pancreatic/breast/ovarian/prostate cancer or personal history of breast/ovarian/prostate cancer (FABRIC study)

• DOI: 10.1007/s10147-020-01721-x
• Publication Date: 2020-06-13T16:02:33Z
• Authors: Naohiro Okano; Chigusa Morizane; Shogo Nomura; Hideaki Takahashi; Hidetaka Tsumura; Hironaga Satake; Nobumasa Mizuno; Kunihiro Tsuji; Kazuhiko Shioji; Akinori Asagi; Kohichiroh Yasui; Sho Kitagawa; Tomomi Kashiwada; Atsushi Ishiguro; Masashi Kanai; Makoto Ueno; Takashi Ogura; Satoshi Shimizu; Kazutoshi Tobimatsu; Masayo Motoya; Koji Nakashima; Masafumi Ikeda; Takuji Okusaka; Junji Furuse
• Keywords: Clinical endpoint

A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers.Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled.Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities.GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended.UMIN000017894.