In patients with treatment-naive metastatic pancreatic cancer, the addition of nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) to gemcitabine improved overall survival vs gemcitabine alone, in an international study presented at the 2013 Gastrointestinal Cancers Symposium.¹

New Standard

“We are very proud of this study and we are confident in this result. We believe that nab-paclitaxel plus gemcitabine is a new standard for the treatment of patients with metastatic pancreatic cancer,” said Daniel Von Hoff, MD, Physician-in-Chief and Distinguished Professor at the Translational Genomics Research Institute (TGen) in Scottsdale, Arizona.

Nab-paclitaxel is approved for the treatment of metastatic breast cancer. Studies with other taxanes in pancreatic cancer have not been encouraging.

“The past few decades have brought us very few treatment advances for patients with advanced pancreatic cancer. I have counted 33 phase III trials since 1990, and only 3 were positive. This has been a frustrating area,” he said in an interview with The ASCO Post.

“The fact that nab-paclitaxel plus gemcitabine demonstrated an overall survival benefit, and also did so at 1 and 2 years, is a significant step forward in offering potential new hope for our patients,” Dr. Von Hoff said. He believes the regimen could also serve as a backbone for the addition of new agents, such as monoclonal antibodies.

Study Details

MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) was an international phase III open-label study in which 861 patients at 151 sites were randomly assigned to receive nab-paclitaxel at 125 mg/m² followed by gemcitabine at 1,000 mg/m² on days 1, 8, and 15 every 4 weeks, or gemcitabine at 1,000 mg/m² weekly for 7 weeks in cycle 1, then on days 1, 8, and 15 every 4 weeks. Treatment with the combination extended median overall survival by approximately 2 months—from 6.7 months with single-agent gemcitabine to 8.5 months with the combination. This represented a highly significant 28% reduction in the risk of dying (P = .000015), Dr. Von Hoff reported.

“Interestingly, we saw a separation of the curves at 2 to 3 months that widened and persisted,” he said. “At each time point along the curve the difference was statistically significant.”

The combination led to significant improvements in a number of outcomes:

• 28% reduction in mortality risk: median overall survival was 8.5 vs 6.7 months (P = .000015)
• 31% reduction in risk of disease progression: median progression-free survival was 5.5 months vs 3.7 months (P = .000024)
• 30% improvement in time to treatment failure: median of 5.1 vs 3.6 months (P < .0001)
• 59% increase in survival at 12 months (P = .00020) and 78% increase at 18 months (P = .00803)
• Improved overall response rate: 23% vs 7%

Superiority across Subgroups

Nab-paclitaxel/gemcitabine was favored in all subgroups. “In fact, the poorer the prognostic factor, the more favorable the hazard ratio,” he said.

Censoring the analysis at the start of second-line (subsequent) therapy produced a more impressive overall survival benefit: median of 9.4 months vs 6.8, a 32% reduction in risk (P = .000072), Dr. Von Hoff reported.

More grade 3/4 adverse events were observed with the combination, most commonly neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%). The neuropathy was “rapidly reversible, and 44% of these patients were able to resume treatment,” he added. Treatment-related deaths occurred in 4% of each arm. ■

Disclosure: Dr. Von Hoff is a consultant for and has received honoraria and research funding from Celgene.

Reference

1. Von Hoff DD, Ervin T, Arena FP, et al:  2013 Gastrointestinal Cancers Symposium. Abstract LBA148. Presented January 25, 2012.