Liposomal Irinotecan (MM-398) Approved in Pancreatic Cancer

Zosia Chustecka

Disclosures

October 22, 2015

A new option is now available for patients with metastatic pancreatic cancer who have previously been treated with gemcitabine-based chemotherapy. The US Food and Drug Administration (FDA) has just approved a novel encapsulated form of irinotecan in a long-circulating nanoliposome (Onivyde, Merrimack Pharmaceuticals, Inc), previously known as MM-398, for use in combination with fluorouracil and leucovorin (multiple brands) for such patients.

The agency granted priority review and orphan drug designation for the product.

The FDA noted that the effectiveness of the product was demonstrated in a three-arm, randomized, open-label study (known as the NAPOLI-1 trial), which was conducted in 417 patients with metastatic pancreatic adenocarcinoma whose cancer had progressed after treatment with gemcitabine (Gemzar, Eli Lilly and Company) alone or in combination with other agents.

The regimen used in the trial was a combination of liposomal irinotecan (80 mg/m² IV over 90 min) administered prior to fluorouracil (2400 mg/m² over 46 hr) and racemic leucovorin (400 mg/m² over 30 min) every 2 weeks.

Patients treated with this combination of liposomal irinotecan plus fluorouracil/leucovorin lived for an average of 6.1 months, compared with 4.2 months for those treated with only fluorouracil/leucovorin in the control group, and 4.2 months for patients in another group who were treated with liposomal irinotecan alone. (This was an experimental arm in the trial; liposomal irinotecan is not approved for use alone in the treatment of metastatic pancreatic cancer.)

There was also an improvement in progression-free survival, to a median of 3.1 months with liposomal irinotecan plus fluorouracil/leucovorin compared with 1.5 months for those receiving fluorouracil/leucovorin.

When the results of the NAPOLI-1 study were presented last year at the World Congress on Gastrointestinal Cancer, lead author Andrea Wang-Gillam, MD, PhD, assistant professor in the Division of Oncology at Washington University in St. Louis, Missouri, said: "Patients with metastatic pancreatic cancer or pancreatic cancer in general have very limited options.

"These patients just simply don't do well," she commented. "This was a positive trial and will provide a new treatment option for patients with metastatic pancreatic cancer."

Updated results from this trial were presented earlier this year at the 2015 Gastrointestinal Cancers Symposium. In these latest results, the median overall survival with the combination of liposomal irinotecan, fluorouracil, and leucovorin was 8.9 months vs 5.9 months with fluorouracil and leucovorin alone (hazard ratio, 0.47; 95% confidence interval, 0.29 - 0.77; P = .0018).

The safety of Onivyde was evaluated in 398 patients, the FDA noted. The most common side effects of treatment with liposomal irinotecan included diarrhea, fatigue, vomiting, nausea, decreased appetite, stomatitis, and pyrexia. There were also reports of lymphopenia and neutropenia, and death due to sepsis following neutropenia has been reported, the agency noted.

Product labeling includes a boxed warning about the risks for severe neutropenia and diarrhea.

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