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Pancreatic cancer is poised to surpass colorectal cancer as the 2nd leading cause of cancer-related deaths in the United States by 2020.[1]With multiple high-profile diagnoses over the past few years vaulting the disease into the public conversation, researchers and the biopharmaceutical industry are focused on gaining a better understanding of this complicated disease.

As one of the most aggressive and deadly cancers, metastatic pancreatic cancer has been viewed as a death sentence upon diagnosis.[2]

This is often attributed to the fact that many patients (more than 52%) are diagnosed in the later stages of disease when the cancer has started to spread to nearby parts of the body. The lack of proven biomarkers makes it extremely difficult to detect the disease in the early stages. Moreover, symptoms, which can range from abdominal or back pain, loss of appetite and digestive problems are non-specific and often associated with other conditions.

Barriers to Treatment
The structure of a pancreatic tumor makes it extremely difficult to develop therapies that can penetrate the dense tissue that surrounds and protects it. As such, the malignant cells often resist therapies, which speaks to why pancreatic cancer has the lowest clinical trial success rate in oncology.

Approved treatment options for pancreatic cancer exist, but when compared to other cancers, patients are less likely to receive treatment following their diagnosis. A recent study published in JNCI Cancer Spectrum showed significant variation in treatment rates for de novo metastatic cancer patients who died within one month of diagnosis. Of the 18,159 pancreatic cancer patients analyzed, only 12.5 percent received at least one treatment modality compared to 37.2 percent of patients with colorectal cancer (n=12,034) (breast cancer n=3,609, 34.9%; lung cancer n= 67,046, 29%).[3] The authors noted the data suggest oncologists may be more likely to recommend treatment for cancer types known to respond more favorably to treatment in terms of overall survival versus cancers where a physician’s ability to predict survival is less clear.

Treatment Sequencing in Metastatic Pancreatic Cancer
Despite these challenges, emerging research on immune-based treatments and therapies that target specific gene mutations continue to show promise among specific subsets of patients.

Current 1st line therapy is comprised of two established chemotherapy regimens, FOLFIRINOX* and gemcitabine + nab-paclitaxel. In clinical practice, the gemcitabine + nab-paclitaxel combination regimen is widely used with newly diagnosed patients.

*A regimen consisting of leucovorin calcium, fluorouracil, irinotecan hydrochloride and oxaliplatin used for the treatment of pancreatic cancer.[4]

The implementation of combination chemotherapies has helped give patients the chance to be on treatment and remain on therapy beyond the first-line. From 2006-2015, the number of patients receiving second-line therapy has increased 18 percent.

For the patients whose disease has progressed following gemcitabine treatment, irinotecan liposome injection (ONIVYDE®) in combination with fluorouracil (5-FU) and leucovorin (LV) has been proven to help patients live longer (Median Overall Survival: 95% CI; 6.1 months vs 4.2 months for 5-FU/LV alone)**.[5] ONIVYDE® in combination with 5-FU/LV is the first and only second-line treatment approved by the Federal Drug Administration in combination with 5-FU/LV for metastatic pancreatic cancer after gemcitabine-based therapy. ONIVYDE® has been shown to extend overall survival by 32% and double progression-free survival (Median PFS: 95% CI; 3.1 months vs. 1.5 months for 5-FU/LV alone).

**NAPOLI‐1 was a global, phase 3, randomized, open‐label, multicenter trial in patients (N=417) with metastatic adenocarcinoma of the pancreas whose disease had progressed following gemcitabine‐based therapy. Patients were initially randomized to receive ONIVYDE® (100 mg/m2 every 3 weeks) or 5‐FU/LV. After 63 patients were enrolled, a third arm, ONIVYDE® (70 mg/m2 every 2 weeks) + 5‐FU/LV, was added. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was median OS. Additional efficacy endpoints were PFS and ORR. There was no improvement in OS for ONIVYDE vs 5-FU/LV (HR=1.00, p=0.97 [2-sided log-rank]).

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


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.

For more Important Safety Information please see the end of the article.

To learn more about Onivyde and how it may help in appropriate metastatic pancreatic cancer, please visit here.

There is no denying the urgency to improve outcomes for patients and continue to work towards a cure. Ipsen is dedicated to continuing research in pancreatic cancer. For the 56,770 people who will be diagnosed with pancreatic cancer in the U.S. this year, every moment matters – whether it’s witnessing the birth of a grandchild, seeing a child get married or an extra day at a favorite destination.[6]


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.


  • ONIVYDE is contraindicated in patients who have experienced a severe hypersensitivity reaction to ONIVYDE or irinotecan HCl


  • 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


  • 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%)


  • 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


  • 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.

[2] SEER Cancer Statistics Factsheets: Pancreas Cancer. National Cancer Institute. Available at: Accessed August 16, 2017.
[3] Sineshaw HM, et al. JNCI Cancer Spectr. 2019;doi:10.1093/jncics/pkz021.
[5] ONIVYDE Full Prescribing Information


ONIVYDE® is a registered trademark of Ipsen Biopharm Limited.
All other trademarks and registered trademarks are property of their respective owners.
© 2019 Ipsen Biopharmaceuticals, Inc.

July 2019 ONV-US-001872