• Oncology Clinical Trials
• Gastrointestinal Cancers

• Oncology Clinical Trials
• Gastrointestinal Cancers

The addition of MM-398 to 5-flurouracil (5-FU) and leucovorin (LV) extended overall survival (OS) and progression-free survival (PFS) in patients with metastatic pancreatic adenocarcinoma (mPAC) who had previously received gemcitabine-based treatment when compared with 5-FU plus LV alone. Andrea Wang-Gillam, MD, PhD, Washington University School of Medicine in St Louis, St Louis, Missouri, USA, presented data from the Study of MM-398 With or Without 5-Fluorouracil and Leucovorin, Versus 5-Fluorouracil and Leucovorin in Patients With Metastatic Pancreatic Cancer [NAPOLI 1; Von Hoff D et al. Ann Oncol. 2014 (abstr O-0003)].

A novel formulation, MM-398 is irinotecan that is encapsulated with a long-circulating nanoliposome. In a Phase 2 trial, MM-398 demonstrated clinical activity in patients with mPAC who had received gemcitabine-based treatment. The purpose of the NAPOLI 1 trial was to further evaluate the safety and efficacy of MM-398 in patients with mPAC.

In the open-label Phase 3 NAPOLI 1 trial, 417 patients with mPAC who had received gemcitabine-based therapy were randomly assigned in a 1:1:1 fashion to receive MM-398 monotherapy, 5-FU plus LV (control arm), or MM-398 plus 5-FU and LV. The primary end point was OS, which was compared with that of the control arm. In the study, 398 patients received treatment. Baseline characteristics were similar among all arms, with head of pancreas and liver metastases present in 61% and 68% of patients, respectively.

Treatment with MM-398 plus 5-FU and LV resulted in significant improvements in OS, PFS, time-to-treatment failure, and overall response rate. In patients who received MM-398 plus 5-FU and LV, median OS was 6.1 months (95% CI, 4.8 to 8.9), compared with 4.2 months (95% CI, 3.3 to 5.3) in patients who received 5-FU and LV alone (HR, 0.67; p = .012). Patients who received MM-398 plus 5-FU and LV experienced a median PFS of 3.1 months (95% CI, 2.7 to 4.2), compared with 1.5 months (95% CI, 1.4 to 1.8) for those in the control arm (HR, 0.56; p < .001). MM-398 monotherapy did not improve any parameters when compared with the control arm.

Grade 3/4 adverse events occurred more frequently in the arm receiving MM-398 plus 5-FU and LV and included a decrease in neutrophil count, as well as fatigue, diarrhea, and vomiting. Other adverse events included febrile neutropenia and sepsis.

In conclusion, Dr Wang-Gillam indicated that, in her opinion, the data from the NAPOLI 1 trial suggest that the addition of MM-398 to 5-FU and LV in patients with mPAC results in a substantial improvement in OS and PFS when compared with 5-FU plus LV alone.

• © 2014 MD Conference Express®