On October 22, 2015, the US Food and Drug Administration (FDA) approved Onivyde (irinotecan liposome injection, Merrimack Pharmaceuticals, Inc.), in combination with fluorouracil (5-FU) and leucovorin, to treat patients with advanced/metastatic pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy.1
There will be approximately 48,960 new cases of pancreatic cancer diagnosed this year in the United States, comprising 2% of all cancers. Yet, pancreatic cancer is one of the most deadly, accounting for over 40,000 deaths this year, making it the fourth deadly cancer in the country. And the incidence is rising.2
The high mortality rate is usually due to late diagnosis – pancreatic cancer generally is not found early enough for effective treatment. The prognosis is such that the National Institutes of Health says that any patient diagnosed with pancreatic cancer, regardless of stage, “can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used.”2
Because of the complexity of pancreatic cancer and the difficulty in finding new treatments (researchers still don’t understand its etiology), new chemotherapeutic agent approvals are few and far between.
Only three therapies have been approved by the FDA over the past 20 years for the treatment of metastatic pancreatic cancer: gemcitabine (Gemzar, 1996), erlotinib (Tarceva) in combination with gemcitabine (2005), and nab-paclitaxel (Abraxane) in combination with gemcitabine (2013).3, 4, 5
Leading to the approval of Onivyde was a phase III, randomized, controlled study of 417 patients with metastatic pancreatic adenocarcinoma, whose cancer had progressed despite receiving gemcitabine or a gemcitabine-based therapy. Three arms evaluated the efficacy of Onivyde plus fluorouracil and leucovorin, Onivyde alone, and fluorouracil and leucovorin without Onivyde.
The results showed that median overall survival increased from 4.2 months for patients who received fluorouracil and leucovorin alone to 6.1 months when Onivyde was added to the protocol. Progression-free survival was also better in the Onivyde group at 3.1 months, compared with 1.5 months for patients in the other group. There was no survival improvement for those who received only Onivyde compared to those who received fluorouracil/leucovorin--Onivyde is not approved for use as a single agent for the treatment of patients with metastatic pancreatic cancer.
The most common adverse events--affecting more than 20% of the patients taking Onivyde--were diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, stomatitis, and pyrexia. The most common severe laboratory abnormalities (more than 10% grade 3 or 4) were lymphopenia and neutropenia. A boxed warning will be included on the labeling due to the risks of severe neutropenia and diarrhea.
- U.S. Department of Health and Human Services. (2015). FDA approves new treatment for advanced pancreatic cancer. U.S. Food and Drug Administration.
- National Cancer Institute. (2015). Pancreatic Cancer Treatment –for health professionals (PDQ®).
- National Cancer Institute. (2013). FDA Approval for Gemcitabine Hydrochloride.
- National Cancer Institute. (2013). FDA Approval for Erlotinib Hydrochloride.
- Mulcahy N. (2013). FDA Approves Nab-Paclitaxel for Pancreatic Cancer. Medscape Multispeciality.