New chemotherapy combination improved OS in metastatic pancreatic cancer

The novel agent MM-398, combined with 5-FU and leucovorin, provided an OS of 6.1 months in patients with metastatic pancreatic cancer — a 1.9-month increase from the 4.2-month survival achieved with 5-FU plus leucovorin alone, according to a press release from Merrimack Pharmaceuticals, makers of MM-398.

Patients included in the phase 3 NAPOLI-1 study were previously treated with a gemcitabine-based therapy across more than 100 sites in North America, South America, Europe, Asia and Australia. The primary log-rank analysis of OS was statistically significant (P=.012) with a corresponding HR of 0.67. A statistically significant advantage for PFS also was observed in the combination arm, according to study results.

Daniel D. Von Hoff

“This demonstration of a survival benefit from the MM-398 plus 5-FU and leucovorin combination is particularly important given that we have very few treatment options for patients in this tough clinical setting,” Daniel D. Von Hoff, MD, FACP, global principal investigator of the NAPOLI-1 study, chief scientific officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center and distinguished professor at Translational Genomics Research Institute, said in a press release.

Patients (n=417) were assigned to one of two MM-398 (irinotecan sucrosofate liposome injection) regimens: 80 mg/m² combined with 5-FU and leucovorin once every 2 weeks or 120 mg/m² as monotherapy once every 3 weeks. Researchers then compared each arm with a control arm of 5-FU and leucovorin alone.

MM-398 as monotherapy resulted in a 4.9-month median OS. However, this did not lead to a statistically significant survival advantage when compared with the 4.2-month median OS in the control arm. The HR for OS was 0.99 (P=.942).

There was an increase in the level of adverse events with MM-398 monotherapy vs. MM-398 plus 5-FU and leucovorin. The rates for grade 3 or higher adverse events in the combination arm were neutropenia (14.5%), fatigue (13.7%), diarrhea (12.8%) and vomiting (11.1%). There was a more than 2% difference between the combination and control arms in sepsis occurrence (3.4%).

“The Pancreatic Cancer Action Network’s goal is to double pancreatic cancer survival by 2020. The positive results of this trial demonstrate progress toward that goal in a disease for which additional treatment options are urgently needed to improve patient outcomes,” Julie Fleshman, president and CEO of the Pancreatic Cancer Action Network, said in the press release. “These results also underscore the important role clinical trials play when patients are exploring their treatment options. We applaud Merrimack’s dedication to improving the treatment landscape for this patient population, and helping us charge forward in the fight against pancreatic cancer.”

The NAPOLI-1 study will be presented in full during the European Society for Medical Oncology World Congress on Gastrointestinal Cancer in Barcelona, Spain, June 25-28, 2014.

A new drug application is expected to be submitted to the FDA for the MM-398 combination regimen this year.