Modified Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin or S-1, Irinotecan, and Oxaliplatin Versus Nab-Paclitaxel + Gemcitabine in Metastatic or Recurrent Pancreatic Cancer (GENERATE, JCOG1611): A Randomized, Open-Label, Phase II/III Trial
Author(s): Akihiro Ohba, MD1; Masato Ozaka, MD2; Junki Mizusawa, PhD3; Takuji Okusaka, MD4; Satoshi Kobayashi, MD5; Taro Yamashita, MD6; Masafumi Ikeda, MD7; Ichiro Yasuda, MD8; Kazuya Sugimori, MD9; Naoki Sasahira, MD2; Kenji Ikezawa, MD10; Ikuya Miki, MD11; Naohiro Okano, MD12; Nobumasa Mizuno, MD13; Masayuki Furukawa, MD14; Hirofumi Shirakawa, MD15; Yusuke Sano, MD16; Hiroshi Katayama, MD16; Junji Furuse, MD5; Makoto Ueno, MD5; on behalf of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG);
PURPOSE
Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) and nab-paclitaxel + gemcitabine are recommended as first-line treatments for metastatic pancreatic cancer. S-1, irinotecan, and oxaliplatin (S-IROX) demonstrated activity in a phase Ib trial in this population. Therefore, these three regimens were directly compared.
METHODS
This randomized phase II/III trial was performed 45 centers in Japan. Eligible patients age 20-75 years with an Eastern Cooperative Oncology Group performance status of 0 or 1 and pathologically confirmed metastatic or recurrent pancreatic cancer were randomly assigned (1:1:1) to receive mFOLFIRINOX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes, l-leucovorin 200 mg/m2 over 2 hours, each once daily on day 1, and fluorouracil 2,400 mg/m2 over 46 hours on days 1-3, every 2 weeks), S-IROX (oxaliplatin 85 mg/m2 over 2 hours, irinotecan 150 mg/m2 over 90 minutes on day 1, and S-1 80 mg/m2/day administered orally twice daily on days 1-7, every 2 weeks), or nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) on days 1, 8, and 15 every 4 weeks. The primary end point was overall survival (OS).
RESULTS
A total of 527 patients were enrolled, with 426 included in the planned interim analysis. The median OS was 14.0 months (hazard ratio [HR], 1.31 [95% CI, 0.97 to 1.77]) and 13.6 months (HR, 1.35 [95% CI, 1.00 to 1.82]) in the mFOLFIRINOX and S-IROX groups, respectively, as compared with 17.1 months in the nab-paclitaxel + gemcitabine group. The predictive probability of achieving superiority in the final analysis was
CONCLUSION
Neither mFOLFIRINOX nor S-IROX appeared to be superior compared with nab-paclitaxel + gemcitabine as the first-line treatment for metastatic or recurrent pancreatic cancer.
Author Affiliations
1Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan; 2Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 3JCOG Data Center, National Cancer Center Hospital, Tokyo, Japan; 4Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo, Japan; 5Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan; 6Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan; 7Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; 8Third Department of Internal Medicine, University of Toyama, Toyama, Japan; 9Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; 10Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan; 11Department of Gastroenterology, Hyogo Cancer Center, Akashi, Japan; 12Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan; 13Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan; 14Department of Hepato-Biliary-Pancreatology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan; 15Department of Hepato-Biliary-Pancreatic Surgery, Tochigi Cancer Center, Utsunomiya, Japan; 16JCOG Operations Office, National Cancer Center Hospital, Chuo, Japan
