242P - Effects of nal-IRI (MM-398) ± 5-fluorouracil on quality of life (QoL) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previous...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Pancreatic Cancer
Presenter Richard Hubner
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors R. Hubner1, A. Cubillo2, J. Blanc3, D. Melisi4, D.D. von Hoff5, A. Wang-Gillam6, L. Chen7, C. Becker8, K. Mamlouk9, B. Belanger10, Y. Yang11, F. de Jong12, J.T. Siveke13
  • 1Medical Oncology, Christie Hospital NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2Start Madrid, Centro Integral Oncologico Clara Campal, Madrid/ES
  • 3Oncology, Hôpital Saint-André, Bordeaux/FR
  • 4Digestive Molecular Oncology, University of Verona, Verona/IT
  • 5Medical Oncology, TGen and Honor Health, Phoenix/Scottsdale/US
  • 6Division Of Oncology, Washington University in St. Louis, St. Louis/US
  • 7Oncology, National Health Research Institutes - National Institute of Cancer Research, Tainan/TW
  • 8Market Access, Merrimack Pharmaceuticals, Inc., Cambridge/US
  • 9Medical Affairs, Merrimack Pharmaceuticals, Inc., Cambridge/US
  • 10Biostatistics, Merrimack Pharmaceuticals, Inc., Cambridge/US
  • 11Global Heor, Oncology, Baxalta Inc., Cambridge/US
  • 12Medical Affairs, Oncology, Shire, Baxalta GmbH, Zürich/CH
  • 13West German Cancer Center, University Hospital Essen, Essen/DE



The randomized phase 3 NAPOLI-1 study showed that nal-IRI + 5-fluorouracil/leucovorin (5-FU/LV) significantly improved overall survival vs 5-FU/LV (6.1 vs 4.2 months; unstratified hazard ratio 0.67; P = 0.012) in patients with mPDAC previously treated with gemcitabine-based therapy (Wang-Gillam et al., Lancet 2016). QoL was a secondary end point of NAPOLI-1.


Patients were to complete the European Organization for Research and Treatment of Cancer quality-of-life core questionnaire (EORTC-QLQ-C30) at baseline, every 6 weeks, and 30 days after follow-up visit. The population analyzed included patients with a baseline and ≥1 post-baseline assessment. In a responder analysis, patients were classified as improved (≥10% improvement from baseline score maintained for ≥6 weeks), worsened (did not meet improvement criteria and died or had ≥10% worsening from baseline score), or stable (not improved or worsened) for each subscale. Pairwise treatment arm comparisons on response classification were performed for each subscale using Cochran-Mantel-Haenszel testing adjusted for multiplicity with a Benjamini-Hochberg correction.


Of 154 evaluable patients in this population, 69% (49/71) of patients in the nal-IRI + 5-FU/LV arm and 53% (44/83) in the 5-FU/LV arm had data at 12 weeks. Median baseline scores for Global Health Status (GHS), Functional and Symptom Scales were similar between arms. The median change in score at 12 weeks was 0 for both treatment arms for GHS and for all Functional and Symptom Scales except for physical functioning and fatigue. The between-arm differences for physical functioning and fatigue were not substantial. Also, there were no significant between-arm differences in the proportion of improved, worsened, or stable patients.


In NAPOLI-1, nal-IRI + 5-FU/LV–treated patients with data through 12 weeks tended to maintain their baseline QoL over the period, and no significant differences versus the 5-FU/LV–treated patients were observed. Study results are limited by the small number of patients and variability in QoL subscale scores.

Clinical trial indentification


Legal entity responsible for the study





J-F. Blanc: Received honoraria from Baxalta. D. Melisi: Served on advisory board for Eli Lilly and received honoraria from Celgene and Roche. D.D. von Hoff: Served as consultant for AlphaMed. A. Wang-Gillam: Received research funding from Newlink, EMD, Pfizer, AstraZeneca, Pricision Biological, BioMed Valley, Halozyme, ChemoCentryx, OncoMed, ADURO, Millennium, Merrimack, Prometheus, and CTI, and served on ad boards for Pfizer and Merrimack. L-T. Chen: Received data monitoring board, statistician, and support of medical writer from Merrimack and honorarium from PharmaEngine, Inc. C. Becker: Employee of Merrimack. K. Mamlouk, B. Belanger: Employee of, own stock in, and have received reimbursement for travel/accommodations/expenses from Merrimack. Y. Yang: Employee of and hold stock options in Baxalta Inc. F. de Jong: Employee of and own stock in Shire. J.T. Siveke: Served on ad board for Merrimack. All other authors have declared no conflicts of interest.