NAPOLI: Using Liposomal Irinotecan (with 5-FU/LV) in the Second-Line Setting in mPDAC and Beyond

Video content above is prompted by the following:

Second-line pancreatic cancer treatment follows established principles of using alternative backbone chemotherapy regimens, typically employing fluorouracil-based therapy after gemcitabine failure or vice versa. The approach avoids triplet regimens in the second line for patients who initially received gemcitabine/nab-paclitaxel, recognizing that doublet selection likely reflected patient-specific factors precluding intensive therapy. Treatment selection in the second line focuses on 2-drug combinations, with 5-fluorouracil/oxaliplatin (FOLFOX) or 5-fluorouracil/irinotecan (FOLFIRI) representing primary options based on adverse effect profiles and patient tolerance.

Molecular tumor sequencing has become essential in pancreatic cancer management, requiring early implementation due to the often rapidly declining performance status in metastatic patients. BRCA mutations represent the most clinically actionable finding, encouraging platinum-based therapy selection, though randomized trial data supporting this approach remain limited. Approximately 96% of patients lack currently actionable mutations beyond BRCA, highlighting the ongoing need for expanded targeted therapy options in pancreatic adenocarcinoma.

The goals of care discussion become increasingly important in second-line treatment, with quality of life considerations taking precedence over pure survival benefit. Treatment continuation depends on clinical symptom improvement, including pain control and energy levels, rather than radiographic response alone. The NAPOLI-1 trial data supporting 5-fluorouracil/liposomal irinotecan in the second line provides evidence-based treatment options, though patient selection remains critical for optimal outcomes and toxicity management.