EFFICACY AND SAFETY STUDIED IN GLOBAL PHASE 3 CLINICAL TRIAL2,4

NAPOLI-1: THE LARGEST PHASE 3 TRIAL IN PATIENTS WITH METASTATIC PANCREATIC CANCER WITH DISEASE PROGRESSION AFTER GEMCITABINE-BASED THERAPY2,4

  • Treatment continued until disease progression or unacceptable toxicity1

Primary endpoint: OS1

  • OS was evaluated using 2 pair-wise comparisons: ONIVYDE vs 5-FU/LV and ONIVYDE+ 5-FU/LV vs 5-FU/LV
    • The comparisons between the ONIVYDE + 5-FU/LV and the 5-FU/LV arms are limited to patients enrolled in the 5-FU/LV arm after the protocol amendment (n=119)

Secondary endpoints: PFS, ORR, and safety1,4

  • Tumor status assessments were conducted at baseline and every 6 weeks thereafter or sooner if investigator suspected disease progression

*Study was amended to add the ONIVYDE + 5-FU/LV arm once safety data on the combination became available; 63 patients already had been enrolled in the original 2-arm study at the time of amendment.1,2

The disease must have progressed after previous gemcitabine-based therapy given in a neoadjuvant, adjuvant (only if distant metastases occurred within 6 months of completing adjuvant therapy), locally advanced, or metastatic setting.2

IV=intravenous; KPS=Karnofsky performance status.

MOST PATIENTS WERE TREATED IN 1ST & 2ND LINE METASTATIC PANCREATIC CANCER AFTER GEMCITABINE1,2

NAPOLI-1: PATIENT CHARACTERISTICS

BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS OF PATIENTS RANDOMIZED TO ONIVYDE + 5-FU/LV ARMS COMBINED2,4

 

ONIVYDE + 5-FU/LV IS APPROVED FOR USE AFTER GEMCITABINE-BASED TREATMENT IN METASTATIC PANCREATIC CANCER1

  • Participants in NAPOLI-1 were evenly distributed across a number of demographic and baseline characteristics, including prior number of therapies, age, sex, and site of metastatic disease1
  • Patients were enrolled at 76 sites in 14 countries across North America, Europe, Asia, South America, and Oceania2

5-FU/LV control group based on protocol version 2.
§Baseline KPS score was missing for one patient in the 5-FU/LV group (enrolled under protocol 2) who was subsequently stratified as having a score ≥90.
||Patients with no prior therapy for metastatic disease were required to have received gemcitabine or gemcitabine-based therapy in the neoadjuvant/adjuvant setting.
KPS=Karnofsky performance status; SD=standard deviation.

Indication and Important Safety Information, incl. Boxed Warning

INDICATION

ONIVYDE® (irinotecan liposome injection) is indicated, in combination with fluorouracil (5-FU) and leucovorin (LV), for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.

Limitation of Use: ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas.

WARNING: SEVERE NEUTROPENIA and SEVERE DIARRHEA

  • Fatal neutropenic sepsis occurred in 0.8% of patients receiving ONIVYDE. Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving ONIVYDE in combination with 5-FU and LV. Withhold ONIVYDE for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment
  • Severe diarrhea occurred in 13% of patients receiving ONIVYDE in combination with 5-FU/LV. Do not administer ONIVYDE to patients with bowel obstruction. Withhold ONIVYDE for diarrhea of Grade 2–4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity
CONTRAINDICATION
  • ONIVYDE is contraindicated in patients who have experienced a severe hypersensitivity reaction to ONIVYDE or irinotecan HCl
WARNINGS AND PRECAUTIONS
  • Severe Neutropenia: See Boxed WARNING. In patients receiving ONIVYDE/5-FU/LV, the incidence of Grade 3/4 neutropenia was higher among Asian (18/33 [55%]) vs White patients (13/73 [18%]). Neutropenic fever/neutropenic sepsis was reported in 6% of Asian vs 1% of White patients
  • Severe Diarrhea: See Boxed WARNING. Severe and life-threatening late-onset (onset >24 hours after chemotherapy [9%]) and early-onset diarrhea (onset ≤24 hours after chemotherapy [3%], sometimes with other symptoms of cholinergic reaction) were observed
  • Interstitial Lung Disease (ILD): Irinotecan HCl can cause severe and fatal ILD. Withhold ONIVYDE in patients with new or progressive dyspnea, cough, and fever, pending diagnostic evaluation. Discontinue ONIVYDE in patients with a confirmed diagnosis of ILD
  • Severe Hypersensitivity Reactions: Irinotecan HCl can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction
  • Embryo-Fetal Toxicity: ONIVYDE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during and for 1 month after ONIVYDE treatment
ADVERSE REACTIONS
  • The most common adverse reactions (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%)
  • The most common Grade 3/4 adverse reactions (≥10%) were diarrhea (13%), fatigue/asthenia (21%), and vomiting (11%)
  • Adverse reactions led to permanent discontinuation of ONIVYDE in 11% of patients receiving ONIVYDE/5-FU/LV; The most frequent adverse reactions resulting in discontinuation of ONIVYDE were diarrhea, vomiting, and sepsis
  • Dose reductions of ONIVYDE for adverse reactions occurred in 33% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring dose reductions were neutropenia, diarrhea, nausea, and anemia
  • ONIVYDE was withheld or delayed for adverse reactions in 62% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring interruption or delays were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia
  • The most common laboratory abnormalities (≥20%) were anemia (97%), lymphopenia (81%), neutropenia (52%), increased ALT (51%), hypoalbuminemia (43%), thrombocytopenia (41%), hypomagnesemia (35%), hypokalemia (32%), hypocalcemia (32%), hypophosphatemia (29%), and hyponatremia (27%)
DRUG INTERACTIONS
  • Avoid the use of strong CYP3A4 inducers, if possible, and substitute non-enzyme inducing therapies ≥2 weeks prior to initiation of ONIVYDE
  • Avoid the use of strong CYP3A4 or UGT1A1 inhibitors, if possible, and discontinue strong CYP3A4 inhibitors ≥1 week prior to starting therapy
USE IN SPECIFIC POPULATIONS
  • Pregnancy and Reproductive Potential: See WARNINGS & PRECAUTIONS. Advise males with female partners of reproductive potential to use condoms during and for 4 months after ONIVYDE treatment
  • Lactation: Advise nursing women not to breastfeed during and for 1 month after ONIVYDE treatment

Please see full Prescribing Information, including Boxed WARNING.

References: 1. ONIVYDE [package insert]. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2017. 2. Wang-Gillam A, Li C-P, Bodoky G, et al. Lancet. 2016;387:545-557. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed May 9, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. 4. Data on file #1. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015. 5. Zhang H. Onco Targets Ther. 2016;9:3001-3007. 6. Kalra AV, Kim J, Klinz G, et al. Cancer Res. 2014;74:7003-7013. 7. Data on file #3. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015.

©2019 Ipsen Biopharmaceuticals, Inc. All rights reserved. March 2019 ONV-US-001533

INTENDED FOR HEALTHCARE PROFESSIONALS

The information contained in this site is intended for US healthcare professionals only.

Please choose an option below to continue.

I am an oncologist/healthcare professional

I am an oncology nurse

I am not a healthcare professional

NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.