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BIBTEX RIS

NAPOLI-1: Randomized Phase 3 Study of MM-398 (NAL-IRI), with or Without 5-Fluorouracil and Leucovorin, Versus 5-Fluorouracil and Leucovorin, in Metastatic Pancreatic Cancer Progressed on or Following Gemcitabine-Based Therapy

2014; Elsevier BV; Volume: 25; Linguagem: Inglês

10.1093/annonc/mdu193.3

1569-8041

Daniel D. Von Hoff, C.P. Li, Andrea Wang‐Gillam, G. Bodoky, Andrew Dean, Gayle Jameson, Teresa Macarulla, K.H. Lee, David Cunningham, Jean‐Frédéric Blanc, Richard Hubner, C.-F. Chiu, Gilberto Schwartsmann, Jens T. Siveke, Fadi Braiteh, Victor Moyo, Bruce Belanger, Navreet Dhindsa, E. Bayever, L.T. Chen,

Cancer Treatment and Pharmacology

Introduction: MM-398 (nal-IRI) is a novel encapsulation of irinotecan in a long-circulating nanoliposome. MM-398 had clinical activity in a Phase 2 study of pts with metastatic pancreatic adenocarcinoma (mPAC) after prior gemcitabine–based therapy. Methods: Pts with mPAC after prior gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS in arms A and C, each vs. the control arm B. Results: A total of 417 patients were randomized, of which 398 received treatment. Baseline characteristics were balanced, 61% head of pancreas, and 68% liver metastases. OS, PFS, TTF, and ORR were significantly improved by MM-398 + 5FU/LV vs. 5FU/LV. Median OS was 6.1m (95% CI: 4.8–8.9) and 4.2m (3.3–5.3), respectively, HR = 0.67, p = 0.012; and median PFS 3.1m (2.7–4.2) and 1.5m (1.4–1.8), respectively, HR = 0.56, p < 0.001. MM-398 alone did not demonstrate a statistical improvement in efficacy. Major grade ≥3 AEs in the MM-398 + 5-FU/LV, MM-398 and 5-FU/LV arms were neutrophil count decreased (23.1%, 15.3%, 3%), fatigue (13.7%, 6.1%, 3.7%), diarrhea (12.8%, 21.1%, 4.5%), and vomiting (11.1%, 13.6%, 3.0%), respectively; neutrophil count decreased was based on lab. values [by investigator report, "neutropenia", (14.5%, 5.4%, 0.7%) and "neutrophil count decreased" (10.3%, 8.2%, 0.7%) respectively]. Additional AEs of interest were febrile neutropenia (1.7%, 4.1%, 0%) and sepsis (3.4%, 2.0%, 0.7%) in MM-398 + 5FU/LV, MM-398 and 5FU/LV respectively.