Updated overall survival analysis of NAPOLI-1: Phase III study of nanoliposomal irinotecan (nal-IRI, MM-398), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #L11
J Clin Oncol 34, 2016 (suppl 4S; abstr 417)
Andrea Wang-Gillam, Chung-Pin Li, Gyorgy Bodoky, Andrew Dean, Yang-Shen Shan, Gayle S. Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Jean-Frédéric Blanc, Richard Hubner, Chang-Fang Chiu, Gilberto Schwartsmann, Jens T Siveke, Fadi S. Braiteh, Victor M. Moyo, Bruce Belanger, Eliel Bayever, Daniel D. Von Hoff, Li-Tzong Chen; Washington University in St. Louis, St. Louis, MO; Taipei Veterans General Hospital, Taipei, Taiwan; St. László Teaching Hospital, Budapest, Hungary; St. John of God Hospital, Subiaco, Australia; National Institute of Cancer Research, National Health Institutes and National Cheng Kung University Hospital, Tainan, Taiwan; TGen, Banner Health, Phoenix, Scottsdale, AZ; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Seoul National University Hospital, Seoul, South Korea; Royal Marsden Hospital, Sutton Surrey, United Kingdom; Hôpital Saint-André, Bordeaux, France; Christie Hospital NHS Foundation Trust, Altrincham, United Kingdom; China Medical University Hospital, Taichung, Taiwan; Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Klinikum Rechts der Isar der TU Muenchen, Munich, Germany; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Merrimack Pharmaceuticals, Inc., Cambridge, MA; National Health Research Institutes, National Institute of Cancer Research, Taipei, Taiwan

Abstract Disclosures


Background: NAPOLI-1 is a global, randomized Phase 3 study evaluating nal-IRI—a nanoliposomal irinotecan—with or without 5-FU/LV in 417 patients with mPAC previously treated with gemcitabine-based therapy. Primary survival analysis was based on 313 events. Nal-IRI+5FU/LV significantly improved overall survival (OS, primary endpoint), 6.1 months (mo) vs 4.2 mo; with 5-FU/LV (unstratified hazard ratio [HR] = 0.67; P = 0.012). Primary endpoint was supported by improved progression-free survival, time to treatment failure, objective response and CA19-9 tumor marker response rates, and manageable toxicities. An updated analysis of OS, 6- and 12-month-survival estimates, and safety is presented. Methods: The updated descriptive analysis of OS, based on 378 events (25 May 2015), includes data from all randomized patients across the 3 arms. Results: After 378 OS events, nal-IRI+5-FU/LV (n = 117) retained an OS advantage relative to 5-FU/LV (n = 119): 6.2 mo (95% confidence interval [CI], 4.8–8.4) vs 4.2 mo (95% CI, 3.3–5.3) with an unstratified HR of 0.75 (P = 0.0417). In contrast, there was no OS advantage with nal-IRI monotherapy (n = 151) vs 5-FU/LV (n = 149): 4.9 mo [95% CI, 4.2–5.6] vs 4.2 mo [95% CI, 3.6–4.9], HR = 1.08; P = 0.5. Six-month survival estimates were 53% (95% CI, 44–62%) for nal-IRI+5-FU/LV vs 38% (95% CI, 29–47%) for 5-FU/LV; 12-month survival estimates were 26% (95% CI, 18-35%) for nal-IRI+5-FU/LV vs 16% (95% CI, 10–24%) for 5-FU/LV. With events in nearly all patients, the OS curves converge at ~20 mo with 19 patients (16.2%) surviving beyond 20 mo. This is a reason for attenuation of the HR estimate and unstratified log rank p-value. The most common grade 3+ adverse events occurring at a ≥ 2% incidence in the nal-IRI-containing arms were neutropenia, diarrhea, vomiting, and fatigue. Conclusions: In an updated analysis, the median OS benefit for nal-IRI+5FU/LV over 5-FU/LV was maintained, with a similar safety profile. Nal-IRI+5-FU/LV may be a new standard of care for patients with mPAC previously treated with gemcitabine-based therapy. Clinical trial information: NCT01494506