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

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.