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New Indication Solidifies Nab-Paclitaxel Pancreatic Regimen

Anita T. Shaffer @Shaffer1
Published: Monday, Oct 28, 2013
Ramesh K. Ramanathan

Ramesh K. Ramanathan, MD

 

Medical Director, Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare
Deputy Director, Translational Research Division at TGen
Scottsdale, AZ

The ability of clinicians to improve treatment outcomes that gemcitabine offers for patients with metastatic pancreatic cancer is expected to move forward now that the FDA has approved a new indication for nab-paclitaxel (Abraxane) as part of a combination regimen, according to researchers.

On September 6, the FDA approved Abraxane in combination with gemcitabine for first-line treatment of patients with adenocarcinoma of the pancreas, which represents approximately 95% of pancreatic tumors. The agent was approved at a recommended dosage of 125 mg/m2 intravenously infused on days 1, 8, and 15 of each 28-day cycle, with gemcitabine administered immediately afterward.

The combination already had been incorporated into the National Comprehensive Cancer Network guidelines as a category 2B recommendation, but has been upgraded to a category 1 classification. The dual therapy “could become the backbone for new regimens” in treatment of the disease, noted Daniel D. Von Hoff, MD, chief scientific officer at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, physician-in-chief at TGen, and lead author of the study, in presenting pivotal clinical trial results at the 2013 Gastrointestinal Cancers Symposium in January.1

Although oncologists have been incorporating the combination into treatment plans, the FDA’s approval makes it a standard of care more likely to be reimbursed by insurance plans, observed Ramesh K. Ramanathan, MD, medical director of the Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare and deputy director of the Translational Research Division at TGen, in an interview. Ramanathan served as the principal investigator of the study for the United States.

Efforts to improve upon the clinical benefits of gemcitabine therapy have been under way for more than 20 years, said Ramanathan. He has been investigating the potential efficacy of an Abraxane combination since 2007 and played a leading role in the research that led to the new indication.

Table. Key Outcomes From the MPACT Trial

  ABRAXANE + gemcitabine
(N = 431)
Gemcitabine (N = 430)
Overall Survival
Number of deaths, n (%) 333 (77) 359 (83)
Median OS (months) 8.5 6.7
95% CI 7.9- 9.5 6.0- 7.2
HR (95% CI) 0.72 (0.62-0.83)
P value <.0001
Progression-free Survival
Death or progression, n (%) 277 (64) 265 (62)
Median PFS (months) 5.5 3.7
95% CI 4.5-5.9 3.6-4.0
HR (95% CI) 0.69 (0.58-0.82)
P value <.0001
Overall Response Rate
Confirmed complete or partial overall response, n (%) 99 (23) 31 (7)
95% CI 19.1-27.2 5.0-10.1
P value <.0001

HR indicates hazard ratio of Abraxane plus gemcitabine versus gemcitabine alone; OS, overall survival; PFS, progression-free survival. Source: Prescribing information.

MPACT Trial Results

Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials was among 151 sites in 11 countries that participated in the pivotal MPACT trial, which accrued from May 2009 and April 2012.

With a primary endpoint of overall survival (OS), 861 patients with stage IV pancreatic cancer who had no prior treatment for metastatic disease were randomized to Abraxane 125 mg/m2, followed by gemcitabine 1000 mg/m2 (n = 431), or gemcitabine alone (n = 430). Patients were treated until their disease progressed, with computed tomography scans performed every 8 weeks.

The median OS was 8.5 months in patients assigned to Abraxane plus gemcitabine, compared with 6.7 months in those assigned to gemcitabine monotherapy. The combination regimen also provided significant improvements in progression-free survival and overall response rates (Table).

Abraxane is an albumin-bound form of paclitaxel with a mean particle size of approximately 130 nanometers. Ramanathan said researchers believe there are two main reasons that the combination is more effective than monotherapy.

“One reason is that Abraxane causes more of the active component of gemcitabine to be present longer in the cancer cells by inhibiting one of the enzymes,” Ramanathan said. “The other reason is that we think Abraxane weakens the shell (called the stroma) around pancreatic cancers. Pancreatic cancers in particular have a very thick stroma. This can prevent chemotherapy from entering the cancer cells. We think Abraxane weakens this outer shell so chemotherapy can get in.”
 
The adverse-event (AE) profile experienced by patients on the combination also was favorable, particularly considering that those participants typically received a larger cumulative dosage for a longer period of time than did patients in the monotherapy arm, investigators indicated.


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