Efficacy and safety of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02, BAX-2398) in patients with metastatic pancreatic cancer in Asia: A subgroup analysis of the phase 3 NAPOLI-1 Study

[[abstract]]Background: The global Phase 3 trial, NAPOLI-1, demonstrated that nal-IRI + 5-fluorouracil and leucovorin (5-FU/LV) significantly improved overall (OS), progression-free survival (PFS) and objective response rate (ORR) vs 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPAC) previously treated with gemcitabine-based therapy. Herein, we present a post hoc subgroup analysis of the Asia cohort in the NAPOLI-1 study. Methods: Pts were randomly assigned (1:1:1) to receive nal-IRI (80 mg/m2, equivalent to 70 mg/m2 of irinotecan base) + 5-FU/LV (2400/400 mg/m2) q2w, nal-IRI (120 mg/m2, equivalent to 100 mg/m2 of irinotecan base) q3w, or 5-FU/LV (2000/200 mg/m2 weekly for weeks 1-4 q6w). The primary endpoint was OS. Results: Of 132 pts randomized in Asian centers, 34 were assigned to treatment with nal-IRI+5-FU/LV, 50 with nal-IRI, and 48 with 5-FU/LV. In the Asia cohort, nal-IRI+5-FU/LV significantly improved median OS versus 5-FU/LV (8.9 vs 3.7 months, P = 0.0281) (Table). Improvements in PFS and ORR were also observed. There were no significant differences in outcomes between 5-FU/LV and nal-IRI monotherapy. Grade ≥3 treatment-emergent adverse events in ≥ 15% of pts in either nal-IRI arm were neutropenia (55%, 34%, and 2% in the nal-IRI+5-FU/LV, nal-IRI, and 5-FU/LV arms, respectively), white blood cell count decreased (21%, 8%, 0%), diarrhea (3%, 16%, 5%), and anemia (18%, 24%, 14%). There were no cases of Grade ≥3 peripheral neuropathy. Conclusions: This subgroup analysis confirmed that nal-IRI+5-FU/LV is an efficacious treatment option with a manageable safety profile in patients with mPAC treated in Asia. Nal-IRI+5-FU/LV may represent a new standard of care for patients with mPAC previously treated with gemcitabine-based therapy