Abstract
BackgroundThere are no head-to-head comparisons evaluating the efficacy of the main polychemotherapy regimens used for patients with pancreatic cancer in the adjuvant setting. We aimed to describe the relative efficacy of modified FOLFIRINOX (mFOLFIRINOX), gemcitabine plus capecitabine (GEM-CAP) and gemcitabine plus nab-paclitaxel (GEM-NAB) in this setting using a Bayesian network approach.MethodsWe collected data from the ESPAC-4, PRODIGE 24 and APACT trials. Disease-free survival (DFS), according to the investigators, and overall survival (OS) for the three polychemotherapy regimens were compared using gemcitabine as the reference arm. We ran Markov chain Monte Carlo simulations with a fixed-effect model to generate the posterior distribution of the hazard ratios (HRs) using non-informative priors. Relative efficacy was measured by HRs, surface under cumulative ranking and rankograms.ResultsmFOLFIRINOX was the chemotherapy regimen most likely to be the most effective in the adjuvant setting (98.9% and 89.6% probability for DFS and OS, respectively). GEM-NAB marginally improved DFS (HR = 0.97, 95% credible interval (95% CrI) = 0.77–1.21) and OS (HR = 0.98, 95% CrI = 0.76–1.25) when compared to GEM-CAP. However, GEM-NAB had the highest chances of being the second most active chemotherapy regimen (61.4% and 52.5% probability for DFS and OS, respectively), whereas GEM-CAP was less likely to represent the second most active regimen (37.7% and 40.1% probability for DFS and OS, respectively).ConclusionFor patients eligible and fit enough to undergo adjuvant treatment with mFOLFIRINOX, this constitutes the treatment of choice. For those with contraindications to mFOLFIRINOX, while both GEM-NAB and GEM-CAP can be considered appropriate alternatives, GEM-NAB is likely the most effective regimen.
Highlights
There are no head-to-head comparisons evaluating the efficacy of the main polychemotherapy regimens used for patients with pancreatic cancer in the adjuvant setting
Publication costs for this article were supported by ecancer (UK Charity number 1176307)
The studies presented similar inclusion and exclusion criteria – Supplementary Table 1. Patients included in these trials should be 18 years old or above, have the pathological diagnosis of ductal adenocarcinoma and have been submitted to microscopically complete (R0) or incomplete (R1) resection
Summary
There are no head-to-head comparisons evaluating the efficacy of the main polychemotherapy regimens used for patients with pancreatic cancer in the adjuvant setting. Data from developed [2, 3] and developing [4] countries suggest that the burden of pancreatic neoplasms in cancer epidemiology is expected to grow significantly in the decade to come. This high lethality rate is partially related to the disease stage at diagnosis. 15%–20% of the patients are candidates for curative-intent surgery [5]. For those submitted to surgery, survival outcomes are dismal when this treatment modality is used in isolation [6]
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