Systemic Chemotherapy as First-line Treatment for Metastatic Pancreatic Adenocarcinoma: A Bayesian Analysis

Abstract

Objective The preferred chemotherapy regimen for metastatic pancreatic cancer remains a matter of controversy. In the present study, we aimed to assess and rank the effectiveness and toxicity of all of the available chemotherapy regimens included in the last 15 years' randomized controlled trials (RCTs) for metastatic pancreatic adenocarcinomas objectively. Methods PubMed, Embase, Cochrane Collaboration database, and ClinicalTrials.gov were searched for RCTs comparing chemotherapy regimens as first-line treatment for metastatic pancreatic adenocarcinomas. Using a Bayesian network meta-analysis, we compared and ranked all included chemotherapy regimens in terms of the overall survival, progression-free survival, response rate, and hematological toxicity. Results We identified 2,206 articles and included in the analysis 46 eligible articles reporting 44 RCTs with a total of 9,133 patients and 48 first-line intravenous systemic chemotherapy regimens. The models showed a good fit to the data. The top-ranked chemotherapy regimen for the overall survival was FP (simplified leucovorin + fluorouracil + nab-paclitaxel), with a hazard ratio (HR) of 0.45 versus gemcitabine monotherapy (95% credible interval 0.28-0.71). The regimen ranked first for the progression-free survival was gemcitabine + erlotinib + bevacizumab (HR 0.39, 0.23-0.62). GS (gemcitabine + S-1) had the highest overall response rate [odds ratio (OR) versus gemcitabine monotherapy 7.06, 1.15-51.15]. GemCape (gemcitabine + capecitabine) + erlotinib was ranked the most hematologically toxic (OR 7.78, 0.75-95.60). Conclusion The available evidence suggests that FP ranked first for metastatic pancreatic cancer in terms of the overall survival. GemCape + erlotinib ranked the most toxic.