Final results of NAPOLI-1: a phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

nal-IRI, a liposomal formulation of irinotecan, plus 5-FU/LV is approved in the US for patients (pts) with mPAC previously treated with gemcitabine-based therapy. Primary analysis (data cutoff, Feb 14, 2014) of the NAPOLI-1 trial (NCT01494506) showed that, after 313 events, nal-IRI + 5-FU/LV significantly improved median overall survival (OS) vs 5-FU/LV (6.1 vs 4.2 mo; HR 0.67; 95% CI 0.49-0.92; P = 0.012; Wang-Gillam et al, Lancet. 2016). Here we report the final analysis of NAPOLI-1 (data cutoff, Nov 16, 2015). 417 pts were randomly assigned to nal-IRI 70 mg/m2 (equivalent to 80 mg/m2 irinotecan HCl trihydrate salt) + 5-FU/LV 2400/400 mg/m2 q2w (n = 117), nal-IRI 100 mg/m2 (equivalent to 120 mg/m2 irinotecan HCl trihydrate salt) q3w (n = 151), or 5-FU/LV 2000/200 mg/m2 weekly for weeks 1-4 q6w (n = 149). Log-rank P values are 2-sided. After 382 events, median OS was improved with nal-IRI + 5-FU/LV vs 5-FU/LV (6.2 vs 4.2 mo; HR 0.75; 95% CI 0.57-0.99; P = 0.038), but not for nal-IRI vs 5-FU/LV (4.9 vs 4.2 mo; HR 1.07; 95% CI 0.84-1.36; P = 0.567). Kaplan-Meier estimates of OS for nal-IRI + 5-FU/LV and 5-FU/LV, respectively, were 53% and 38% at 6 mo, and 26% and 16% at 12 mo. Median progression-free survival was longer for nal-IRI + 5-FU/LV vs 5-FU/LV (3.1 vs 1.5 mo; HR 0.57; 95% CI 0.43-0.76; P < 0.001), but not for nal-IRI vs 5-FU/LV (2.7 vs 1.6 mo; HR 0.81; 95% CI 0.63-1.04; P = 0.111). Response rates per RECIST v1.1 were higher for nal-IRI + 5-FU/LV vs 5-FU/LV (17% vs 1%; P < 0.001) and for nal-IRI vs 5-FU/LV (6% vs 1%; P = 0.020). Grade ≥3 treatment-emergent adverse events in ≥10% of pts in either nal-IRI arm were neutropenia (28%, 15%, and 1% in the nal-IRI + 5-FU/LV, nal-IRI, and 5-FU/LV arms, respectively), fatigue (14%, 6%, and 4%), diarrhea (13%, 21%, and 5%), vomiting (12%, 14%, and 4%), anemia (9%, 11%, and 7%), and hypokalemia (3%, 12%, and 2%). Final results from NAPOLI-1 continue to show OS benefit for nal-IRI + 5-FU/LV vs 5-FU/LV. No new safety concerns were identified. nal-IRI + 5-FU/LV provides a new treatment option for pts with mPAC previously treated with gemcitabine-based therapy.