Adding MM-398, a novel nanoliposome formulation of irinotecan, to standard treatment improves survival for metastatic pancreatic cancer patients who have already received gemcitabine.
This study was presented at the European Society for Molecular Oncology (ESMO) 16th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
Drug delivery is one of the biggest challenges in the treatment of pancreatic cancer. MM-398 is anticancer drug irinotecan encapsulated in a nanoliposome, a microscopic bubble made out of the same material as cell membranes. Nanoliposomes can be filled with drugs and then targeted to specific locations in the body such as tumors.
“This delivery system allows longer drug exposure in the circulation, leading to higher accumulation of the drug and its active metabolite at the tumor site,” said study author Andrea Wang-Gillam, MD, assistant professor in the Division of Oncology at Washington University in St. Louis, Missouri. “MM-398 generated higher antitumor activity and was more effective than conventional irinotecan alone.”
The phase II study demonstrated that MM-398 had clinical activity as a second-line treatment in patients with metastatic pancreatic cancer refractory to gemcitabine.
The phase III NAPOLI-1 study was a global randomized trial with almost 400 patients who had progressive pancreatic cancer or who had received gemcitabine-based therapy. There were three treatment arms: MM-398 alone, standard treatment with 5-fluorouracil (5FU)/leucovorin, and MM-398 plus 5FU/leucovorin. Overall survival was the primary end point.
Overall survival was improved significantly with the combination therapy of MM-398 plus 5FU/leucovorin compared to 5FU/leucovorin alone. Median overall survival was 6.1 months in the MM-398 plus 5FU/leucovorin group compared with 4.2 months in the group receiving standard treatment with 5FU/leucovorin alone. Progression-free survival also improved significantly: 3.1 months in patients receiving MM-398 plus 5FU/leucovorin, up from 1.5 months in patients who received standard therapy. MM-398 alone did not provide any additional survival benefit over standard therapy.
Wang-Gillam said: “The results are very exciting because the trial met its primary end point and found a statistically significant benefit of MM-398 plus 5FU/leucovorin on overall survival and progression-free survival compared to 5FU/leucovorin alone. We also found a significant benefit of the combination therapy on overall response rate and biochemical response.”
However, combination therapy led to more gastrointestinal side effects (diarrhea, vomiting) than standard treatment alone.
NAPOLI-1 showed that MM-398 plus 5FU/leucovorin was an effective second-line therapy for metastatic pancreatic cancer. “This provides a new treatment option for patients with metastatic pancreatic cancer,” said Wang-Gillam.
This study was published in Annals of Oncology (2014; doi:10.1093/annonc/mdu193.3).