Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: subgroup analysis of the NAPOLI-1 study.

The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR]=0.67, p=0.012). Here, we report efficacy and safety results from a post-hoc subgroup analysis of patients treated at Asian centers. This analysis included patients from Asia. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients at Asian centers receiving nal-IRI+5-FU/LV (n=34) had significantly longer median OS vs 5-FU/LV (n=35) (8.9 vs 3.7 months; unstratified HR=0.51, p=0.025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV vs 5-FU/LV (4.0 vs 1.4; unstratified HR=0.48, p=0.011), and increased ORR (8.8% vs 0; p=0.114). nal-IRI monotherapy (n=50) numerically improved efficacy endpoints vs 5-FU/LV (n=48): median OS was 5.8 vs 4.3 months (HR=0.83, p=0.423) and median PFS was 2.8 vs. 1.4 months (HR=0.69, p=0.155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV vs 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).