Expanded analyses of NAPOLI-1: Phase 3 study of nal-IRI (MM-398), with or without 5-fluorouracil (5FU) and leucovorin (LV), versus 5-fluorouracil and leucovorin (5FU/LV), in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy

Richard Hubner1,Li-Tzong Chen2,3,Daniel D. Von Hoff4,5,Chung-Pin Li6,7,Andrea Wang-Gillam8,György Bodoky9,Andrew Dean10,Yan-Shen Shan2,3,Gayle Jameson5,11,Teresa Macarulla12,13,Kyung-Hun Lee14,Jean-Frédéric Blanc15,Chang-Fang Chiu16,Gilberto Schwartsmann17,Jens T. Siveke18,Fadi S. Braiteh19,Victor M. Moyo20,Bruce Belanger20,Eliel Bayever20,David Cunningham21

1The Christie NHS Foundation Trust, Manchester, UK,2National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan,3National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan,4HonorHealth, Scottsdale, AZ, USA,5TGen, Scottsdale, AZ, USA,6Taipei Veterans General Hospital, Taipei, Taiwan,7National Yang-Ming University, Taipei, Taiwan,8Washington University in St. Louis, St. Louis, MO, USA,9St László Teaching Hospital, Budapest, Hungary,10St John of God Hospital, Subiaco, Western Australia, Australia,11Scottsdale Healthcare, Scottsdale, AZ, USA,12Vall d’Hebron University Hospital, Barcelona, Spain,13Vall d’Hebron Institute of Oncology, Barcelona, Spain,14Seoul National University Hospital, Seoul, Republic of Korea,15Hôpital Saint-André, Bordeaux, France,16China Medical University Hospital, Taichung, Taiwan,17Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil,18Klinikum rechts der Isar der TU München, Munich, Germany,19Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA

Presenting date: Wednesday 4 November


Nal-IRI is a nanoliposomal encapsulation of irinotecan. OS in the ITT-population was significantly longer with nal-IRI+5FU/LV over 5FU/LV alone (median OS for nal-IRI+5FU/LV was 6.1m (95%CI=4.8-8.9m; N=117) vs 4.2m (95%CI=3.3-5.3m; N=119) for 5FU/LV (unstratified HR=0.67; 95%CI=0.49-0.92; log-rank test p=0.012). Most frequent grade 3+ AEs included neutropenia, fatigue, and GI-effects (diarrhea and vomiting).1 Expanded, pre-specified analyses of the Phase-3 study have been presented.2


Patients with mPAC (n=417) previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) Nal-IRI (120mg/m2 IV over 90min) q3w; (B) 5FU (2,000mg/m2 over 24h) plus racemic LV (200mg/m2 over 30min) x4w followed by 2w rest; or (C) combination of nal-IRI (80mg/m2 IV over 90min) prior to 5FU (2,400mg/m2 over 46h) and racemic LV (400mg/m2 over 30min) q2w. The primary endpoint was OS. The Intent to Treat (ITT)-population included all randomized patients; the Per Protocol (PP)-population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria.


Analysis of the PP-populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination nal-IRI+5FU/LV over the control 5FU/LV arm. Median OS in the PP-population for nal-IRI+5FU/LV-arm was 8.9m (95%CI=6.4-10.5m; N=66) vs 5.1m (95%CI=4.0-7.2m; N=71) for 5FU/LV (unstratified HR=0.57; 95%CI=0.37-0.88; log-rank test p=0.011). The nal-IRI-monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9, consistently favored OS for the nal-IRI+5FU/LV arm over the 5FU/LV arm.


Expanded analysis of the PP-population and sensitivity analyses support the favorability of nal-IRI+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506.3