To view this email as a web page, go here.

To make sure you continue to receive this e-newsletter, please add info@iononline.com to your address book.

specialty-spotlight-hero
 
Full Prescribing Information, including Boxed Warning for ONIVYDE®
Scroll down for complete Important Safety Information
     
ONIVYDE Review of the data for a combination treatment regimen in metastatic Pancreatic cancer FOLLOWING GEMCITABINE-BASED THERAPY
 
George Kim Get Full Contents on Any Device George Kim, MD
University of Florida Health
21st Century Oncology
Jacksonville, Florida

Dr. Kim has been compensated by Ipsen Biopharmaceuticals, Inc. to discuss the clinical data in this program.
 
Pancreatic cancer is rare,1 and because it is often diagnosed at the locally advanced or metastatic stage, it is challenging to treat and typically has a poor prognosis.2 Pancreatic cancer is the third most common cause of cancer-related deaths. 3 Even more dire is the 2.7% 5-year survival for metastatic disease.2

ONIVYDE® (irinotecan liposome injection) is the first and only FDA-approved regimen in combination with 5-FU/LV for the treatment of patients with metastatic pancreatic cancer after disease progression following gemcitabine-based therapy.4
 
INDICATION AND IMPORTANT SAFETY INFORMATION
FOR ONIVYDE
 
INDICATION
 
ONIVYDE 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 (irinotecan liposome injection). 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.
         
         
 
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) *
Liposomal irinotecan + 5-FU and LV is the only Category 1 recommendation from the
National Comprehensive Cancer Network® (NCCN®) for second-line therapy in patients with metastatic pancreatic cancer previously treated with gemcitabine-based therapy in patients with good performance status, defined as an ECOG score 0 to 1 with patent biliary stent and adequate nutritional intake.5
 
An Encapsulation of Irinotecan in a Long-Circulating Liposome
The design of ONIVYDE® features approximately 80,000 irinotecan molecules encapsulated in a longcirculating liposome with a half-life of 25.8 hours.4 In mice bearing human tumor xenografts, irinotecan liposome administered at irinotecan HCl-equivalent doses that were 5-fold lower than irinotecan HCl achieved similar intratumoral exposure of SN-38.4
 
image4
 
NAPOLI-1 was the pivotal phase 3 clinical trial used in the ONIVYDE® approval. This was a large, global, multicenter, open-label, randomized clinical trial of ONIVYDE®+ 5-FU/LV in patients with metastatic pancreatic cancer whose disease had progressed following gemcitabine-based therapy.4
 
NAPOLI-1 Study Outcome Measures
The primary endpoint of NAPOLI-1 was overall survival (OS).4 Key secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety.4 Tumor response assessments were performed every 6 weeks.4
 
NAPOLI-1: Extended OS
ONIVYDE® + 5-FU/LV demonstrated a statistically significant 1.9-month increase in OS: 6.1 months versus 4.2 months with the control arm, as seen here.4 The hazard ratio for this difference was 0.68 (95% CI: 0.50, 0.93; log-rank p=0.014).4 Of note, there was no improvement in OS for ONIVYDE ® monotherapy versus 5-FU/LV.4
 
Graph
 
The probability of survival at 1 year was 24% with ONIVYDE® + 5-FU/LV versus 17% with 5-FU/LV alone.6

NAPOLI-1: Increased PFS
Secondary Endpoint

For the secondary endpoint of PFS, ONIVYDE® + 5-FU/LV resulted in a median PFS of 3.1 months vs. 1.5 months for 5-FU/LV in the control arm 0.55 (95% CI 0.41, 0.75).6
 
Graph
 
Regarding ORR, another secondary endpoint, ONIVYDE® + 5-FU/LV resulted in an ORR of 7.7% (9 of 117) compared with <1% (1 of 19) for 5-FU/LV.4

The median duration of therapy in the ONIVYDE® + 5-FU/LV arm of the NAPOLI-1 was 8.7 weeks.4 The median duration of therapy was also 8.7 weeks for the 5-FU/LV arm.4

NAPOLI-1: Safety Profile
The most common adverse reactions (≥20%) for ONIVYDE® + 5-FU/LV were diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, stomatitis, and pyrexia.4

The most common Grade 3/4 laboratory abnormalities (≥10%) for ONIVYDE® + 5-FU/LV were lymphopenia and neutropenia.4
 
Get Full Contents on Any Device
 
*See the NCCN Guidelines for Pancreatic Adenocarcinoma for a complete list of recommended treatment options.
 
INDICATION AND IMPORTANT SAFETY INFORMATION
FOR ONIVYDE
 
INDICATION
 
ONIVYDE 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 (irinotecan liposome injection). 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
 
ONIVYDE can cause severe or life-threatening neutropenia and fatal neutropenic sepsis. In a clinical study, the incidence of fatal neutropenic sepsis was 0.8% among patients receiving ONIVYDE, occurring in 1/117 patients in the ONIVYDE+ 5-FU/LV arm and 1/147 patients receiving ONIVYDE as a single agent. Severe or life-threatening neutropenia occurred in 20% of patients receiving ONIVYDE + 5-FU/LV vs 2% of patients receiving 5-FU/LV. Grade 3/4 neutropenic fever/neutropenic sepsis occurred in 3% of patients receiving ONIVYDE + 5-FU/LV, and did not occur in patients receiving 5-FU/LV. 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
 
ONIVYDE can cause severe and life-threatening diarrhea. Do not administer ONIVYDE to patients with bowel obstruction. Severe and life-threatening late-onset (onset >24 hours after chemotherapy) and early-onset diarrhea (onset ≤24 hours after chemotherapy, sometimes with other symptoms of cholinergic reaction) were observed. An individual patient may experience both early- and late-onset diarrhea.
 
In a clinical study, Grade 3/4 diarrhea occurred in 13% of patients receiving ONIVYDE + 5-FU/LV vs 4% receiving 5-FU/LV. Grade 3/4 late-onset diarrhea occurred in 9% of patients receiving ONIVYDE + 5-FU/LV vs 4% in patients receiving 5-FU/LV; the incidences of early-onset diarrhea were 3% and no Grade 3/4 incidences, respectively. Of patients receiving ONIVYDE + 5-FU/LV, 34% received loperamide for late-onset diarrhea and 26% received atropine for early-onset diarrhea.
 
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
 
Based on animal data with irinotecan HCl and the mechanism of action of ONIVYDE, ONIVYDE can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during and for 1 month after ONIVYDE treatment.

ADVERSE REACTIONS
 
The most common (≥20%) adverse reactions in which patients receiving ONIVYDE + 5-FU/LV experienced a ≥5% higher incidence of any Grade vs the 5-FU/LV arm, were diarrhea (any 59%, 26%; severe 13%, 4%) (early diarrhea [any 30%, 15%; severe 3%, 0%], late diarrhea [any 43%, 17%; severe 9%, 4%]), fatigue/asthenia (any 56%, 43%; severe 21%, 10%), vomiting (any 52%, 26%; severe 11%, 3%), nausea (any 51%, 34%; severe 8%, 4%), decreased appetite (any 44%, 32%; severe 4%, 2%), stomatitis (any 32%, 12%; severe 4%, 1%), pyrexia (any 23%, 11%; severe 2%, 1%).
     
Of less common (<20%) adverse reactions, patients receiving ONIVYDE + 5-FU/LV who experienced Grade 3/4 adverse reactions at a ≥2% higher incidence of Grade 3/4 toxicity vs the 5-FU/LV arm, respectively, were sepsis (3%, 1%), neutropenic fever/neutropenic sepsis (3%, 0%), gastroenteritis (3%, 0%), intravenous catheter-related infection (3%, 0%), weight loss (2%, 0%), and dehydration (4%, 2%).
     
The laboratory abnormalities in which patients receiving ONIVYDE + 5-FU/LV experienced a ≥5% higher incidence vs the 5-FU/LV arm, were anemia (any 97%, 86%; severe 6%, 5%), lymphopenia (any 81%, 75%; severe 27%, 17%), neutropenia (any 52%, 6%; severe 20%, 2%), thrombocytopenia (any 41%, 33%; severe 2%, 0%), increased alanine aminotransferase (any 51%, 37%; severe 6%, 1%), hypoalbuminemia (any 43%, 30%; severe 2%, 0%), hypomagnesemia (any 35%, 21%; severe 0%, 0%), hypokalemia (any 32%, 19%; severe 2%, 2%), hypocalcemia (any 32%, 20%; severe 1%, 0%), hypophosphatemia (any 29%, 18%; severe 4%, 1%), hyponatremia (any 27%, 12%; severe 5%, 3%), increased creatinine (any 18%, 13%; severe 0%, 0%).
     
ONIVYDE can cause cholinergic reactions manifesting as rhinitis, increased salivation, flushing, bradycardia, miosis, lacrimation, diaphoresis, and intestinal hyperperistalsis with abdominal cramping and early-onset diarrhea. Grade 1/2 cholinergic symptoms other than early diarrhea occurred in 12 (4.5%) ONIVYDE-treated patients.
     
Infusion reactions, consisting of rash, urticaria, periorbital edema, or pruritus, occurring on the day of ONIVYDE administration were reported in 3% of patients receiving ONIVYDE or ONIVYDE + 5-FU/LV.
     
The most common serious adverse reactions (≥2%) of ONIVYDE were diarrhea, vomiting, neutropenic fever or neutropenic sepsis, nausea, pyrexia, sepsis, dehydration, septic shock, pneumonia, acute renal failure, and thrombocytopenia.
     
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
 
Advise pregnant women of the potential risk to a fetus. Advise males with female partners of reproductive potential to use effective contraception during and for 4 months after ONIVYDE treatment.
 
Lactation
 
Advise nursing women not to breastfeed during and for 1 month after ONIVYDE treatment.
 
Pediatric
 
Safety and effectiveness of ONIVYDE have not been established in pediatric patients.

DOSAGE AND ADMINISTRATION
 
The recommended dose of ONIVYDE is 70 mg/m2 intravenous (IV) infusion over 90 minutes every 2 weeks, administered prior to LV and 5-FU. The recommended starting dose of ONIVYDE in patients known to be homozygous for the UGT1A1*28 allele is 50 mg/m2 administered by IV infusion over 90 minutes. There is no recommended dose of ONIVYDE for patients with serum bilirubin above the upper limit of normal. Premedicate with a corticosteroid and an anti-emetic 30 minutes prior to ONIVYDE. Withhold ONIVYDE for Grade 3/4 adverse reactions. Resume ONIVYDE with reduced dose once adverse reaction recovered to ≤Grade 1. Discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction and in patients with a confirmed diagnosis of ILD.
 
Do not substitute ONIVYDE for other drugs containing irinotecan HCl.
 
Please see Full Prescribing Information, including Boxed Warning, for ONIVYDE.
 
References:
     
1. National Cancer Institute. SEER Cancer Statistics Review, 1975-2014. Bethesda, MD.
https://seer.cancer.gov/csr/1975_2014/results_merged/sect_22_pancreas.pdf. Accessed August 1, 2017.
     
2. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts: Pancreas Cancer. Bethesda, MD.
https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed August 1, 2017.
     
3. American Cancer Society. Cancer Facts & Figures 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures /2017/cancer-facts-and- figures-2017.pdf. Accessed August 1, 2017.
     
4. ONIVYDE® [package insert]. Ipsen Biopharmaceuticals, Inc.; 2017.
     
5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.3.2017. © National Comprehensive Cancer Network, Inc.; 2017. All rights reserved. Accessed October 3, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.
     
6. Data on file, Ipsen Biopharmaceuticals, Inc.; 2017.
 
     
image8
Contact Us    Privacy Policy     Terms of Use
     
© 2018 Ipsen Biopharmaceuticals, Inc.
All rights reserved. April 2018 ONV-US-000949
ONIVYDE® is a registered trademark of Ipsen Biopharm Ltd.
     

This email was sent to: Amy.Gonsuron@iononline.com

This email was sent by: ION Solutions, An AmerisourceBergen Company
3101 Gaylord Parkway Frisco, TX 75034 USA


We respect your right to privacy - view our policy

This communication is intended to keep ION members current on late breaking events. It may contain confidential information such as pricing, rebate, and other discount arrangements being provided exclusively to ION members, and as such is intended solely for the use of the addressee. If the reader of this message is not the intended recipient, you are hereby notified that any dissemination, copying, distribution or other use of this material is strictly prohibited. In the event that you have received this material in error, or wish to opt-out of any future emails, please Go Here or notify the sender immediately via email or telephone at 866-565-1070 and destroy all copies. Thank you.