Effect of NALIRIFOX in Asian patients (pts) with treatmentnaive metastatic pancreatic adenocarcinoma (mPAC): Results from the NAPOLI 3 trial

초록

Background NAPOLI 3, a global, randomized, phase 3 study, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) for NALIRIFOX vs gemcitabine+nab-Paclitaxel (Gem+NabP) in pts with mPAC. The aim of this post-hoc analysis is to evaluate the effects of NALIRIFOX in the Asian subgroup (AG) of NAPOLI 3. Methods In the NAPOLI 3 the pts had a confirmed PAC not previously treated in the metastatic setting and with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0/1. They were randomized to NALIRIFOX (liposomal irinotecan 50 mg/m2+ 5-FU 2400 mg/m2 + leucovorin 400 mg/m2+ oxaliplatin 60 mg/m2 on days 1 and 15 of a 28-day cycle) or Gem+NabP (Gem 1000 mg/m2 + NabP 125 mg/m2 on days 1, 8, and 15 of a 28-day cycle). Primary endpoint was OS. Secondary endpoints included PFS, ORR and safety; 383 pts were randomized to NALIRIFOX and 387 to Gem+NabP. Median follow-up was 16.1 months (mts). Results 38 Asian pts (mean age 60.3 years; 60.5% male) were enrolled from Korean and non-Asian sites. Baseline characteristics were balanced between the two treatment arms; Asian pts had a worse ECOG PS and a lower CA 19.9 level vs the general population (GP). In the AG, NALIRIFOX significantly prolonged OS vs Gem+NabP (hazard ratio [HR] 0.31; 95% CI 0.10-0.98). The median OS in NALIRIFOX arm was 14.5 mts in the AG and 11.1 mts in the GP. PFS was also prolonged vs Gem+NabP (HR 0.59; 95% CI 0.21–1.60). The median PFS in NALIRIFOX arm was 10 mts in the AG and 7.4 mts in the GP. In the AG, ORR rate was 70% in NALIRIFOX arm and 41.8% in the GP. In the AG, the incidence of grade ≥3 adverse events (≥G3 AEs) in NALIRIFOX arm was 50% and was 62.2% in the GP. In NALIRIFOX arm, the AG had more ≥G3 hematological events than the GP (40% vs 33%) and fewer ≥G3 non-hematological events in the NALIRIFOX arm than the GP (20.0% vs 42.2%) including ≥G3 diarrhea (5% vs 20.3%). Conclusions The effect of NALIRIFOX in AG was consistent with the GP of NAPOLI 3. NALIRIFOX had a manageable safety profile with a slightly higher incidence of severe hematological events and lower incidence of severe diarrhea.