OBJECTIVES: Management of metastatic pancreatic ductal adenocarcinoma (mPDAC) is very challenging resulting in modest outcomes compared to other common cancers in Europe. For many years, gemcitabine was the standard systemic therapy available to patients with mPDAC. This research aimed to indirectly compare pegylated liposomal irinotecan, 5-fluorouracil, leucovorin (nal-IRI/5-FU/LV) and oxaliplatin regimen (FOLFOX) for second-line mPC in patients who have received gemcitabine-based chemotherapy, standard of care selected by INFARMED for the reimbursement assessment.

METHODS: A systematic literature review (SLR) identified all relevant randomized controlled trials of nal-IRI/5-FU/LV and FOLFOX. Indirect comparisons of overall survival (OS), progression-free survival (PFS), time to quality-of-life deterioration (EORTC-QLQ-C30) and grade 3-4 treatment-emergent adverse events (TEAE) and treatment discontinuation due to AEs were performed based on unadjusted anchored Bucher method, matching-adjusted indirect treatment comparison (MAIC), and simulated treatment comparison (STC) were performed.

RESULTS: The SLR identified seven randomized controlled trials of which two met the inclusion criteria for the quantitative analysis. Anchored Bucher method, MAIC and STC resulted in significant improvements in terms of OS, PFS and time to quality-of-life deterioration with nal-IRI/5-FU/LV vs. FOLFOX, with a risk of death reduced by 54% (hazard ratio [HR]=0.46, 95% CI: 0.26, 0.79) to 56% (HR=0.44, 95% CI: 0.26, 0.76); PFS improved by: Bucher HR=0.57 (95% CI: 0.35, 0.95); MAIC HR=0.58 (95% CI: 0.35, 0.96); STC HR=0.60 (95% CI: 0.36, 0.99); and time to quality-of-life deterioration by: Bucher HR=0.61 (95% CI: 0.27, 1.35); MAIC HR=0.67 (95% CI: 0.30, 1.51). The odds of grade 2-4 TEAEs and treatment discontinuation due to AEs were respectively 69% (MAIC OR=0.31; 95% CI: 0.09, 1.00) and 90% (Bucher OR=0.10; 95% CI: 0.03, 0.38) lower with nal-IRI/5-FU/LV, respectively.

CONCLUSIONS: Pegylated liposomal irinotecan combination is more efficacious and has a better safety profile than FOLFOX for the treatment of metastatic pancreatic cancer in patients who have progressed following gemcitabine-based therapy.