In a phase 1–2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer.
Dr Daniel Von Hoff and colleagues conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer.
The researchers randomly assigned patients with a Karnofsky performance-status score of 70 or more to nab-paclitaxel followed by gemcitabine on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy weekly for 7 of 8 weeks, and then on days 1, 8, and 15 every 4 weeks.
Patients received the study treatment until disease progression.
The researchers' primary end point was overall survival.
|Febrile neutropenia occurred in 3% versus 1% of the patients in the 2 groups|
|New England Journal of Medicine|
Secondary end points were progression-free survival and overall response rate.
A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine or gemcitabine.
The research team's median overall survival was almost 9 months in the nab-paclitaxel–gemcitabine group as compared with 7 months in the gemcitabine group.
The team found that survival rate was 35% in the nab-paclitaxel–gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years.
The researchers observed that median progression-free survival was 6 months in the nab-paclitaxel–gemcitabine group, as compared with 4 months in the gemcitabine group.
The response rate according to independent review was 23% versus 7% in the 2 groups.
The most common adverse events of grade 3 or higher were neutropenia, fatigue, and neuropathy.
The team found that febrile neutropenia occurred in 3% versus 1% of the patients in the 2 groups.
In the nab-paclitaxel–gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days.
Dr Von Hoff's team concludes, "In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased."