Predicting response for each component of the FOLFIRINOX regimen in pancreatic cancer patients

FRAUNHOFFER NICOLAS A.; TEYSSEDOU, CARLOS; BIGONNET, MARTIN; PESSAUX, PATRICK; DUSETTI, NELSON; IOVANNA, JUAN

Encuentro; European Pancreatic Club; 2023

Background Recently, we have successfully developed a transcriptomic signature that can predict the response to gemcitabine treatment in patients with pancreatic ductal adenocarcinoma (PDAC) who have undergone surgery (PMID: 36178036) and in those with metastatic PDAC (PMID: 36496056). This was achieved using a complex approach that combined several preclinical PDAC models. The FOLFIRINOX regimen (FFX) consisting of 5-Fluorouracil (5FU), Oxaliplatin, and Irinotecan is the more effective treatment option, but the high toxicity limits its use for all patients. In this study, we developed and analyzed three different transcriptomic signatures for the drugs composing FFX separately and evaluated their clinical utility.Methods We combined the transcriptomic data of 14 patients derived xenograft (PDX) and 31 patients derived cell cultures (PDC) with their corresponding chemotherapy response profiles. We developed three different predictive signatures as previously reported for the Gemcitabine signature (GemCore; PMID: 36178036). The extracted signatures were then validated in a pooled cohort of 167 patients with advanced/metastatic disease. The pooled cohort was composed by 94 patients from COMPASS cohort and, 73 patients from a new cohort of patients.Results From the total cohort, 111 patients were assessable for the progression-free survival (PFS), In the FFX arm (n=63), for 5FU 15 patients were sensitive and 48 resistant with a median PFS of 8.7 months (CI, 6.1- not reached [NR]) (HR, 0.25; CI, 0.11-0.57; P=0.001), and 3.6 months (CI, 2.7-5.5), respectively. For oxaliplatin 29 patients were sensitive with a median PFS of 8.5 months (CI, 5.3-12.4) (HR, 0.27; CI, 0.13-0.57; P