Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.