Folfirinox Relative Dose Intensity (Rdi) And Disease Control In Advanced Pancreatic Cancer Patients (Apc)

Most APC patients (pts) treated with FOLFIRINOX experience adverse events requiring dose reductions. Lee et al. have described an association between RDI reduction and lower disease control rate (DCR) in Korean APC pts (Lee, EJC, 2017). We aimed to validate these findings in a European setting. We included all consecutive incident APC pts treated with >=3 cycles of FOLFIRINOX, who had at least 1 CT assessment, between 2011 and 2018 in 6 French centres. Imaging was centrally reviewed according to RECIST 1.1. We computed the RDI before 1st evaluation for each component of FOLFIRINOX (5-fluorouracil bolus, 5FUb; 5-fluorouracil infusion, 5FUiv; irinotecan; oxaliplatin), as well as for the combined cumulative RDI (cRDI) of FOLFIRINOX using the modified Hryniuk model (http://www.rdicalc.com). The association between RDI and DCR at 1st evaluation was assessed by multivariate logistic regression models, controlling for clinical factors, number of cycles before evaluation and centre. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the discrimination ability of the models with or without RDI. Same approach was used for response rate (RR). We included 243 patients: 65 with locally advanced and 178 with metastatic disease. Median RDI was 75%, 85%, 81% and 79% for 5FUb, 5FUiv, oxaliplatin and irinotecan, respectively. Median cRDI was 80%. At 1st evaluation, 49 pts had achieved an objective response (RR=20%) and 131 had a stable disease (DCR=74%). The 1-y PFS and 1-y OS were 36% and 55%, respectively. We confirmed that performance status (1 vs 0) and liver metastases were significantly associated with low DCR. None of the RDI were found significantly associated with DCR (p=0.80, p=0.96, p=0.55, p=0.97, p=0.58, for 5FUb, 5FUiv, irinotecan, oxaliplatin, and cRDI, respectively). Including RDI in the model did not improve the ability to predict disease control: AUC=0.79 (95%CI, 0.73 – 0.85) with RDI vs AUC=0.78 (95%CI, 0.72 – 0.85) without. Similar results were observed for RR. RDI of each FOLFIRINOX’s component and cRDI were neither associated with DCR, nor with RR. Pharmacological data would help interpret this finding.