Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years.

// Bradley R. Hall 1, 2 , Andrew Cannon 2 , Pranita Atri 2 , Christopher S. Wichman 3 , Lynette M. Smith 3 , Apar K. Ganti 4, 5 , Chandrakanth Are 1 , Aaron R. Sasson 6 , Sushil Kumar 2 and Surinder K. Batra 2, 7 1 Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE, USA 2 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA 3 Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA 4 Department of Internal Medicine, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, USA 5 Department of Internal Medicine, Division of Hematology and Oncology, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA 6 Department of Surgery, Division of Surgical Oncology, Stony Brook School of Medicine, Stony Brooke, NY, USA 7 Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA Correspondence to: Surinder K. Batra, email: sbatra@unmc.edu Keywords: pancreatic ductal adenocarcinoma; meta-analysis; metastasis; chemotherapy; survival Received: December 09, 2017 Accepted: March 09, 2018 Published: April 10, 2018 ABSTRACT Background: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. Materials and methods: All Phase 2–4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. Results: Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). Conclusions: Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. Funding: The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586).