First-line chemotherapy regimens for locally advanced and metastatic pancreatic adenocarcinoma: a Bayesian analysis

Shuisheng Zhang,1,2 Weimin Xie,3 Yinghua Zou,4 Shuanghua Xie,5 Jianwei Zhang,1 Wei Yuan,6,7 Jie Ma,6–8 Jiuda Zhao,9 Cuiling Zheng,10 Yingtai Chen,1 Chengfeng Wang1 1Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 2Department of General Surgery, Peking University Third Hospital, 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 4Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, 5Department of Cancer Epidemiology and Health Statistics, 6State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 7Clinical Immunology Center, Chinese Academy of Medical Science, 8Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Beijing, 9Department of Medical Oncology, Affiliated Hospital of Qinghai University, Xining, 10Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Background: Systemic chemotherapy is the standard treatment for locally advanced and metastatic pancreatic cancer, but there is no consensus on the optimum regimen. We aimed to compare and rank the locally advanced and metastatic pancreatic adenocarcinoma chemotherapy regimens evaluated in randomized controlled trials (RCTs) in the past 15 years.Materials and methods: PubMed, Embase, Cochrane Collaboration database, and ­ClinicalTrials.gov were searched for RCTs comparing chemotherapy regimens as first-line treatment for locally advanced and metastatic pancreatic adenocarcinomas. By using Bayesian network meta-analysis, we compared and ranked all included chemotherapy regimens in terms of overall survival, progression-free survival, response rate, and hematological toxicity.Results: The analysis included 68 RCTs, with 14,908 patients and 63 treatment strategies. For overall survival, NSC-631570 (hazard ratio [HR] vs gemcitabine monotherapy 0.44, 95% credible interval: 0.24–0.76) and gemcitabine+NSC-631570 (HR 0.45, 0.24–0.86) were the two top-ranked chemotherapy regimens. For progression-free survival, PEFG (cisplatin + epirubicin + fluorouracil + gemcitabine) ranked first (HR 0.51, 0.34–0.77). PG (gemcitabine + pemetrexed) (odds ratio [OR] 4.68, 2.24–9.64) and FLEC (fluorouracil + leucovorin + epirubicin + carboplatin) (OR 4.52, 1.14–24.00) were ranked the most hematologically toxic, with gastrazole having the least toxicity (OR 0.03, 0.00–0.46).Conclusion: The chemotherapy regimens NSC-631570 and gemcitabine+NSC-631570 were ranked the most efficacious for locally advanced and metastatic pancreatic adenocarcinomas in terms of overall survival, which warrants further confirmation in large-scale RCTs. Keywords: locally advanced and metastatic pancreatic adenocarcinoma, chemotherapy regimen, overall survival, ran