Analysis of NAPOLI-1 Study Shows MM-398 Benefit in Metastatic Pancreatic Cancer

An analysis of the phase 3 NAPOLI-1 trial supports the benefits of adding MM-398 chemotherapy for the treatment of patients with metastatic pancreatic cancer who were previously treated with Gemzar (gemcitabine).

In the per-protocol assessment, treatment with the nanoliposomal encapsulation of irinotecan (MM-398) plus 5-fluorouracil plus leucovorin (5-FU/LV) improved overall survival by 53 percent compared with 5-FU/LV alone. In the full intent-to-treat population of NAPOLI-1, MM-398 plus chemotherapy improved survival by 43 percent as reported in 2014.

“In the per-protocol population, the MM-398 plus 5-FU/LV combination regimen achieved a median overall survival of 8.9 months,” said Li-Tzong Chen, of the National Institute of Cancer Research in Tainan City, Taiwan, who reported the expanded pre-specified per-protocol and sensitivity analyses of the NAPOLI-1 data at the 2015 Gastrointestinal Cancers Symposium.

MM-398 contains about 80,000 molecules of irinotecan stably encapsulated in a 100-mm liposome.

“Not surprisingly, the combination achieved a highly significant improvement in overall survival in the per-protocol analysis. But more surprisingly, it also significantly improved overall survival in the non-per-protocol population versus the control arm,” Chen said. “Analysis of the subgroups consistently favored overall survival for the MM-398 plus 5-FU/LV arm over 5-FU/LV alone.”

No benefit was observed for MM-398 as a single agent, with median OS of 4.9 months, compared to 4.2 months with 5-FU/LV.

Dose reductions were necessary for 33 percent of the MM-398 arm versus 3 percent of the control arm, and dose delays occurred in 61 percent versus 21 percent, respectively. In spite of this, the average duration of exposure was 21 weeks for the combination versus 13 weeks for 5-FU/LV alone, Chen indicated.

The safety profile of the combination regimen was considered manageable. In the per-protocol population, the most frequent moderate to severe adverse events were neutropenia, fatigue, diarrhea and vomiting.

Laura Goff, MD, of Vanderbilt University Medical Center, Nashville, commented as the study discussant that the partial response rate of 16 percent in a second-line population was “provocative,” and the median survival times were similar to those previously reported for FOLFIRI (fluorouracil, leucovorin, irinotecan) in second-line pancreatic cancer.

“MM-398 appears to have activity in combination with 5-FU/leucovorin in previously treated pancreas cancer, and it has received fast track status from the FDA,” Goff indicated.

In November 2014, the FDA granted MM-398 plus 5-FU and leucovorin a fast track designation as a second-line treatment for patients with metastatic pancreatic cancer, based on data from the NAPOLI-1 study.