693P - Time course of selected treatment emergent adverse events (TEAEs) in NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Pancreatic Cancer
Presenter Richard Hubner
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors R.A. Hubner1, L. Chen2, J.T. Siveke3, C. Li4, G. Bodoky5, A. Dean6, Y. Shan7, G.S. Jameson8, T. Macarulla9, K. Lee10, D. Cunningham11, J. Blanc12, C. Chiu13, G. Schwartsmann14, F. Braiteh15, K. Mamlouk16, B. Belanger16, F. de Jong17, D.D. von Hoff8, A. Wang-Gillam18
  • 1Department Of Medical Oncology, Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2National Institute Of Cancer Research, National Health Research Institutes, 704 - Tainan/TW
  • 3University Hospital Essen, West German Cancer Center, Essen/DE
  • 4Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei/TW
  • 5Medical Oncology, St. László Teaching Hospital, 1097 - Budapest/HU
  • 6Cancer Services, St John of God Hospital, 6008 - Subiaco/AU
  • 7National Cheng Kung University, National Cheng Kung University Hospital, Tainan/TW
  • 8Medical Oncology, TGen, Phoenix/US
  • 9Oncology Service, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 10Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 11Gi & Lymphoma Unit, Royal Marsden Hospital, SM2 5PT - Sutton/GB
  • 12Hepato-gastroenterology And Digestive Oncology, Hôpital Saint-André, Bordeaux/FR
  • 13Cancer Center, China Medical University Hospital, Taichung/TW
  • 14Ufrgs, Hospital de Clínicas de Porto Alegre, Porto Alegre/BR
  • 15Medicine, Comprehensive Cancer Centers of Nevada, 89169 - Las Vegas/US
  • 16Medicine, Merrimack Pharmaceuticals, Inc., Cambridge/US
  • 17Medicine, Baxalta GmbH, Zürich/CH
  • 18Medicine, Washington University School of Medicine, St. Louis/US

Abstract

Background

Liposomal irinotecan (nal-IRI) plus 5-FU/LV is approved in the US for patients (pts) with mPAC previously treated with gemcitabine-based therapy. Primary analysis from NAPOLI-1 (NCT01494506) showed a significant median survival advantage for nal-IRI + 5-FU/LV 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). The most common TEAEs included diarrhea, vomiting, nausea, decreased appetite, fatigue, neutropenia, and anemia. Here we report incidence and prevalence of selected TEAEs over time in NAPOLI-1.

Methods

Pts were randomly assigned to nal-IRI + 5-FU/LV, nal-IRI, or 5-FU/LV. In this post hoc analysis (data cutoff, Feb 14, 2014), incidence (ie, first occurrence) and prevalence (ie, first occurrence, ongoing event, or recurrence) of selected TEAEs were analyzed by treatment period (first 6 wk [period 1], second 6 wk [period 2], and beyond second 6 wk [period 3]). Denominators for percentages were the number of pts in the risk set during each period (for incidence: pts still on treatment without a previous event; for prevalence: all safety-evaluable pts).

Results

398 pts were treated with nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 147), or 5-FU/LV (n = 134). In the nal-IRI + 5-FU/LV arm, most first occurrences of neutropenia, diarrhea, nausea, and vomiting were during the first 6 wk of treatment, with incidence and severity generally decreasing thereafter (Table). Similarly, prevalence and severity were highest in the first 6 wk and tended to decrease over time. Similar trends were observed in the nal-IRI and 5-FU/LV arms.

Incidence, % nal-IRI + 5-FU/LV nal-IRI 5-FU/LV
Period Period Period
1 2 3 1 2 3 1 2 3
Neutropenia grade n = 117 n = 73 n = 34 n = 147 n = 95 n = 43 n = 134 n = 111 n = 43
1 1 3 3 1 2 0 1 0 0
2 8 3 3 8 3 0 1 2 2
3 14 4 9 5 1 0 2 0 0
4 7 0 0 6 2 0 0 0 0
5 0 0 0 0 0 0 0 0 0
Diarrhea grade n = 117 n = 51 n = 24 n = 147 n = 46 n = 11 n = 134 n = 89 n = 32
1 21 4 0 25 11 18 15 5 6
2 17 12 4 20 7 9 2 1 0
3 12 0 4 16 4 0 2 1 3
4 0 0 0 1 0 0 0 0 0
5 0 0 0 1 0 0 0 0 0
Nausea grade n = 117 n = 56 n = 28 n = 147 n = 53 n = 25 n = 134 n = 87 n = 26
1 21 5 7 23 4 8 19 4 12
2 16 0 7 27 4 8 5 4 4
3 7 2 0 5 2 0 2 2 0
4 0 0 0 0 0 0 0 0 0
5 0 0 0 0 0 0 0 0 0
Vomiting grade n = 117 n = 61 n = 35 n = 147 n = 61 n = 28 n = 134 n = 89 n = 29
1 19 5 11 27 2 7 16 2 4
2 14 0 9 10 3 4 5 1 4
3 10 0 3 12 2 0 1 1 4
4 0 0 0 0 0 0 0 0 0
5 0 0 0 0 0 0 0 0 0

Conclusions

Neutropenia, diarrhea, nausea, and vomiting typically first occur early during the course of treatment with nal-IRI + 5-FU/LV and tend to decrease in incidence and severity thereafter.

Clinical trial identification

NCT01494506

Legal entity responsible for the study

Merrimack Pharmaceuticals, Inc.

Funding

Merrimack Pharmaceuticals, Inc.

Disclosure

L-T. Chen: 1. Merrimack/ NAPOLI-1 study Steering Committee Member, uncompensated 2. Baxalta/ Advisory Meeting, honorarium 3. PharmaEngine/ Consultant, honorarium. J.T. Siveke: 1. Baxalta/ Ad Board, honoraria. A. Dean: Merrimack/ Investigator meeting, travel grant. D. Cunningham: Amgen, AstraZeneca, Bayer, Celgene, Medimmune, Merck Serono, Merrimack, Sanofi: research funding to my institution. J-F. Blanc: Baxalta, honoraria. F. Braiteh: Merrimack, institutional research funding.

K. Mamlouk: Merrimack, employee and stock. B. Belanger: Merrimack, employee. F. de Jong: Baxalta, employee and stock. D.D. von Hoff: Merrimack/ Clinical trial. A. Wang-Gillam: 1. Merrimack/ Ad Board 2. Newlink/ Ad Board 3. Pfizer/ Ad Board. All other authors have declared no conflicts of interest.