Rare Disease Reports: FDA Approves Onivyde for Pancreatic Cancer

November 7, 2015

The FDA has approved Onivyde (irinotecan liposome injection), in combination with fluorouracil and leucovorin, to treat patients with advanced (metastatic) pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy.

The therapy was approved based on the data from the phase 3 NAPOLI-1 trial, a 3-arm, randomized, open label study of patients with metastatic pancreatic adenocarcinoma whose cancer had grown after receiving the chemotherapeutic drug gemcitabine or a gemcitabine-based therapy.

Clinical Trial Data

NAPOLI-1 demonstrated a 1.9-month improvement in overall survival (OS) with the addition of Onivyde to 5-FU and leucovorin. In the combination arm, the median OS was 6.1 months compared with 4.2 months with 5-FU and leucovorin alone (HR, 0.57; 95% CI, 0.41-0.80; P = .0009).

In the international trial, 417 patients with gemcitabine-refractory metastatic pancreatic cancer were randomized to Onivyde monotherapy, 5-FU with leucovorin (control), or Onivyde plus 5-FU and leucovorin. Per standard irinotecan protocols, dexamethasone and a 5-HT3 antagonist could be administered in the combination arms.

In the control, 5-FU was administered at 2000 mg/m2 with racemic leucovorin at 200 mg/m2 every 4 weeks followed by 2 weeks of rest (n = 149). In the combination arm, intravenous Onivyde was administered at 80 mg/m2 prior to 5-FU at 2400 mg/m2 and racemic leucovorin at 400 mg/m2 every 2 weeks (n = 117). In the monotherapy group, MM-398 was administered at 120 mg/m2 every 3 weeks (n = 151).

Adverse Effects

The safety of Onivyde was evaluated in 398 patients who received either Onivyde with fluorouracil/leucovorin, Onivyde alone or fluorouracil/leucovorin. In patients receiving at least one dose of Onivyde, the most commonly reported grade ≥3 adverse events (AEs) with the combination were neutropenia (20%), fatigue (14%), diarrhea (13%), vomiting (11%), nausea (8%), asthenia (8%), and abdominal pain (7%). To address these concerns, MM-398 was approved along with a boxed warning regarding severe neutropenia and diarrhea.

“Many FDA staff who review drug applications are clinicians as well, so it’s especially rewarding when we are able to expedite access to new treatments for patients with unmet needs,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “By using the Priority Review designation for the application for Onivyde, patients will have earlier access to a drug that helps extend survival.”


FDA approves new treatment for advanced pancreatic cancer [news release]. U.S. Food and Drug Administration: October 22, 2015.

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