22 | wetenschapsdag 2023 Sessie 1a: Viatris: Pantastische Pancreas-Perikelen x1 Auteurs J. R. Puik, L. N.C. Boyd, M. Ali, T. Y.S. Le Large, L L. Meijer, H. W.M. van Laarhoven, E. Giovannetti, G. Kazemier Abstract titel Predictive value of miR-379 for response to first-line chemotherapy in advanced pancreatic cancer Background Firstl line systemic treatment of patients with advanced pancreatic ductal adenocarcinoma (PDAC) consists of combined chemotherapeutic regimens of FOLFIRINOX or gemcitabine with nab-paclitaxel. Drug resistance, however, hampers the success and benefit that patients can experience from these chemotherapeutic strategies. Predictive biomarkers are necessary to guide individualized clinical decision-making. This study assesses the value of miRNAs to predict response to FOLFIRINOX vs gemcitabine-nab-paclitaxel in advanced PDAC. Methods Next-generation sequencing was used for biomarker discovery in 24 pre-treatment serum samples from metastatic PDAC patients treated with FOLFIRINOX or gemcitabine-nab-paclitaxel. The top 4 candidate biomarkers (miR-127, miR-155, miR-200, and miR379) were validated by PCR in a separate cohort of 37 patients with advanced PDAC. Cox regression models and ridge regression models were used to assess the association between miRs and the therapy effect of FOLFIRINOX vs gemcitabine-nab¬-paclitaxel in terms of overall survival. Results In the validation cohort, higher miR-379 was strongly predictive of treatment efficacy (interaction test, P=0.0004), and remained predictive after correction for confounding by age and sex. FOLFIRINOX was significantly better than gemcitabine-nabpaclitaxel in the subset of patients with lower than median miR-379 (hazard ratio, 0.32 [95% confidence interval, 0.08 to 0.98]; P=0.046), while gemcitabine-nab-paclitaxel was superior in the subset of patients with higher than median miR-379 (hazard ratio, 0.28 [0.10 to 0.86]; P=0.027). In contrast, there was no evidence for an association between therapy response and miR-155 or miR-200 levels (interaction test, P=0.36 and P=0.19, respectively), while miR127 was moderately predictive of treatment effects (interaction test, P=0.036). Conclusion Pursuant to further validation in larger observational studies, miR379 could serve as a predictive biomarker to guide individualized clinical decision-making between FOLFIRINOX and gemcitabinenab-paclitaxel for patients with advanced PDAC.
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