Hellenic Evaluation of the Long-Term Safety and Efficacy of NalIriFOx as a 1st-line Therapy in Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

Pancreatic cancer is an aggressive malignancy with a dismal prognosis, often diagnosed at an advanced stage where curative treatment options are limited. It is the seventh leading cause of cancer-related deaths globally, with a five-year survival rate of less than 10%.

Progress with systemic therapy for patients with advanced pancreatic cancer has historically been slow. However, therapeutic advances in the past 12 years have resulted in modest yet tangible improvements for patients.

Current first-line treatment options for metastatic pancreatic cancer include combination chemotherapy regimens such as FOLFIRINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel.

FOLFIRINOX has demonstrated significant improvements in overall survival and progression-free survival compared to gemcitabine alone, albeit with increased toxicity. Although FOLFIRINOX has achieved longer median OS compared to gemcitabine - nab-Paclitaxel, its poor toxicity profile made its use very difficult in clinical practice. Therefore, FOLFIRINOX has practically been substituted by the better tolerated modified FOLFIRINOX which has not been formally tested in a randomized clinical trial. Therefore, it remains a need for more effective and better-tolerated first-line therapies for metastatic pancreatic cancer patients.

Liposomal irinotecan or nal-IRI, also known as pegylated liposomal irinotecan and abbreviated as MM-398 or PEP02, has emerged as the only registered post-gemcitabine treatment in mPDAC, often used in the second line after a gemcitabine-based first -line regimen. Nal-IRI is an intravenous liposomal formulation that encapsulates the topoisomerase I inhibitor irinotecan in a lipid-bilayer vesicle.