WASHINGTON, DC—Nanoparticle albumin-bound paclitaxel, often referred to as nab-paclitaxel, combined with gemcitabine boosts survival when given as first-line treatment in patients with advanced pancreatic cancer, according to results released at the 101st annual meeting of the American Association for Cancer Research.
“Our study found that the combination of nab-paclitaxel at the maximum tolerated dose plus gemcitabine more than doubled the length of survival that has been reported with solo gemcitabine, which is the treatment standard in this population,” said Daniel Von Hoff, MD, FACP, physician-in-chief and senior investigator at the Translational Genomics Research Institute in Phoenix, Arizona.
Von Hoff presented findings in 67 patients treated with the combination of nanoparticle albumin-bound paclitaxel and gemcitabine as part of a phase 1/2 open-label study. Nanoparticle albumin-bound paclitaxel is a novel formulation of paclitaxel that allows for the preferential delivery of active drug to the site of the tumor.
“Pancreatic cancer has the worst survivorship of any cancer in the world, with a 1-year survival rate in metastatic disease of about 15% and a 2-year survival rate of less than 5%,” Von Hoff said.
Presently, the disease affects approximately 259,000 people worldwide and more than 42,000 people in the United States.
In the phase 1 dose-escalation portion of the study, nanoparticle albumin-bound paclitaxel (100 mg/m2, 125 mg/m2, 150 mg/m2) in combination with gemcitabine 1000 mg/m2 was administered weekly for 3 weeks with 1 week of
rest. The 125-mg/m2 dose was identified as the maximum tolerated dose.
Of 44 patients who were treated with nanoparticle albumin-bound paclitaxel at the maximum tolerated dose with gemcitabine 1000 mg/m2, the median overall length of survival was 12.2 months. “To date, the longest survival that has been reported with gemcitabine alone has been 5.65 months,” Von Hoff said.
Of patients treated with the combination therapy, the overall response rate was 50% and the disease control rate was 68%. A disease control rate was defined as a complete response, partial response, or stable disease for 16 weeks or longer according to response evaluation criteria in solid tumor criteria.
Overall, three patients in the study population of 67 had a complete response.
Also, all patients who had nanoparticle albumin-bound paclitaxel at the recommended dose who were screened for the tumor marker carbohydrate antigen (CA) 19-9 had a decrease in tumor marker level of a magnitude that has been shown to correlate with improved overall survival. CA 19-9 has been shown to be highly specific and sensitive for pancreatic cancer.
Notably, about two thirds of patients had CA 19-9 decreases of greater than 70%, which correlated with a median overall survival of 15.6%. “This is very dramatic,” Von Hoff noted. “In fact, our study team involving doctors, research nurses, data managers, and so on come from very well-respected cancer centers and have ‘deep’ clinical experience, and we have never seen this level of activity before.”
The nanoparticle albumin-bound paclitaxel–gemcitabine combination is now being tested in patients with advanced pancreatic cancer in a phase 3 trial. “Although there have been a lot of false starts in the past and we’re acutely aware of that possibility, we’re definitely encouraged by our findings,” he said.