Adjuvant therapy in pancreatic adenocarcinoma: A systemic review and meta-analysis.

330 Background: The “optimal” adjuvant treatment in pancreatic cancer remains undetermined. Chemotherapy (chemo) such as gemcitabine (Gem), 5-fluorouracil (5-FU) and chemo-radiotherapy (chemoRT) with either Gem or 5-FU have been investigated in trials. We performed a systematic review and meta-analysis to determine the overall efficacy of adjuvant treatment. Methods: We searched databases (PubMed, Medline, Cochrane database) and major conference proceedings up until August 2015 for randomized trials comparing chemo or chemoRT versus (vs) observation, two different chemo regimens and chemoRT vs chemo. Primary end point was overall survival (OS); secondary end points were relapse free survival (RFS), grade 3/4 toxic effects and quality of life (QoL). We performed meta-analysis as per the PRISMA guidelines; hazard ratios (HR) for OS and RFS were pooled with random-effects modelling. Results: Fifteen trials were identified evaluating 4348 patients. For trials comparing chemo to observation (7 trials, n = 1383) the OS HR was 0.77 (95% CI 0.67-0.89, p = 0.001) and PFS HR 0.73 (95% CI 0.53-1.01, p = 0.06) both favouring chemo. For trials investigating Gem (2 trials, n = 472), OS was improved with HR 0.76 (95% CI 0.63 -0.92, p = 0.006) as was RFS (HR 0.56, 95% CI 0.46-0.68, p < 0.00001). For trials investigating agents other than Gem (5 trials, n = 911), OS was improved with HR 0.79 (95% CI 0.63-0.99, p = 0.04), but RFS was not (2 trials only, HR 1.00, 95% CI 0.73-1.37, p = 0.99). Five trials (n = 1832) compared different chemo regimens to Gem in each case; pooled OS HR was 0.90 (95% CI 0.65-1.25, p = 0.54) and RFS HR 0.88 (95% CI 0.67-1.15, p = 0.35). Insufficient data was available to pool grade 3/4 toxicity for chemo vs observation trials; no significant difference was found in incidence of overall grade 3/4 toxicity for trials comparing two chemo regimens (OR 0.98, 95% CI 0.39-2.47, p = 0.96). QoL data was available in 3 trials (ESPAC-1, ESPAC-3, CapRi) with no significant differences noted. Conclusions: Adjuvant chemo vs no chemo for resected pancreatic adenocarcinoma improves OS and RFS. Adjuvant ChemoRT vs no treatment is not beneficial. Overall, novel chemo regimens have not been shown to be superior to Gem. Reporting of QoL is inadequate to make any conclusion.