Liposomal irinotecan + 5‑fluorouracil/leucovorin (5-FU/LV) is approved for adults with metastatic pancreatic ductal adenocarcinoma following progression with gemcitabine-based therapy. We report results from an open-label phase 1/2 study (NCT02551991) of adults with untreated, unresectable, locally advanced/metastatic-PDAC receiving liposomal irinotecan + 5-FU/LV + oxaliplatin (NALIRIFOX).
Eligible patients were adults with ECOG performance status (PS)≤ 1 and adequate organ function who received NALIRIFOX (liposomal irinotecan 50mg/m2 (free-base), 5-FU 2400mg/m2, LV 400mg/m2, oxaliplatin 60mg/m2) on days 1 and 15 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included progression-free-survival (PFS), overall survival (OS), best overall response, overall response rate (ORR), 16-week disease control rate (DCR16) and duration of response (DoR). RECIST v1.1 was assessed at 8-week screenings and treatment end.
32 patients were included (median [range] age 58.0 [39–76] years; 43.8% men; 87.5% metastatic disease; 56.3% ECOG PS 1). 22 patients experienced grade ≥3 treatment-emergent-adverse-events (TEAEs): neutropenia (31.3%), febrile neutropenia (12.5%), hypokalemia (12.5%), diarrhea (9.4%), nausea (9.4%) and decreased neutrophil count (9.4%). 17 patients had serious TEAEs: nausea (9.4%) and febrile neutropenia (9.4%). TEAEs led to 3 deaths (none treatment-related), dose-adjustment in 26 and discontinuation in 8 patients. Median (95% CI) PFS and OS were 9.2 (7.69–11.96) months and 12.6 (8.74–18.69) months, respectively. One patient, with locally advanced disease, had complete response, 10 partial response, and 15 stable disease. ORR (95% CI) was 34.4 (18.6–53.2)%, DCR16 was 71.9 (53.3–86.3)% and median (95% CI) DoR was 9.4 (3.52, NE) months.
First-line NALIRIFOX raised no new safety signals in patients with locally advanced/metastatic PDAC; anti-tumour activity was promising. The randomized phase-3 NAPOLI-3 study (NCT04083235) will compare NALIRIFOX with gemcitabine + nab-paclitaxel.
This study is funded by Ipsen.
This abstract was originally presented virtually at the 2020 ESMO World Congress on Gastrointestinal Cancer.