Meta-analysis comparing the incidence of serious adverse events, overall survival, and progression-free survival in patients with pancreatic adenocarcinoma harboring unresectable tumors treated with modified FOLFIRINOX or FOLFIRINOX regimen.

person Vuong N. Trieu Sapu Bioscience LLC., Agoura Hills, CA info_outline Vuong N. Trieu, Sanjive Qazi, Seymour H. Fein, Anthony Ernest Maida, Tenshang Joh

Authors person Vuong N. Trieu Sapu Bioscience LLC., Agoura Hills, CA info_outline Vuong N. Trieu, Sanjive Qazi, Seymour H. Fein, Anthony Ernest Maida, Tenshang Joh Organizations Sapu Bioscience LLC., Agoura Hills, CA, Oncotelic Therapeutics, Agoura Hills, CA Abstract Disclosures Research Funding No funding sources reported Background: The evolution of first-line treatment for advanced pancreatic adenocarcinoma (PDAC) from Gemcitabine-based therapies to FOLFIRINOX-based regimens (fluorouracil, leucovorin, irinotecan, oxaliplatin) have demonstrated significant improvements in survival outcomes, however, this was associated with increased side effects such as neuropathy, fatigue, and diarrhea due to its heightened potency. Modified versions of FOLFIRINOX (mFOLFIRINOX) have since been developed with lower doses and longer breaks between cycles to manage side effects. Methods: To systematically test the efficacy and side effects of mFOLIFINOX treatment, we conducted a meta-analysis relating FOLFIRINOX treatment with modified FOLFIROX on the frequency of Grade 3 or 4 adverse events reported in published literature (9 studies), and Serious Adverse Events (SAE) recorded from clinical trials (17 arms accessed from clinicaltrials.gov) in PDAC patients with unresectable tumors. Results: For adverse events occurring in greater than 10% of patients, significant reductions in the frequency of patients experiencing the following events were observed in PDAC patients treated with mFOLFIRINOX: Neutropenia (29.31 % (226/771 patients across 8 arms) versus 18.8% (144/766 across 8 arms; Fisher Exact test, 2-tailed, P < 0.001)), Anorexia (18.57 % (44/237 across 3 arms) versus 5.39% (18/334 across 3 arms); P < 0.001), Peripheral sensory neuropathy (10.63 % (27/254 across 2 arms) versus 3.45% (4/116 across 2 arms); P = 0.025)), and Fatigue (10.57 % (83/785 across 9 arms) versus 6.77% (55/812 across 8 arms); P = 0.007)). Examination of 8 studies (N = 635) for PDAC patients treated with FOLFIRINOX exhibited a median OS time of 11.37 (Range = 10.07 - 13.9) months. Patients treated with mFOLFIRINOX (N = 475) exhibited a median OS time of 12.8 (10.2 - 14.4) months (Two-sample Wilcoxon test, P = 0.372). Conclusions: In conclusion, modified FOLFIRINOX has maintained similar efficacy while reducing severe adverse events, making it more tolerable for adjuvant treatment after surgery.

Pre-clinical