Nab-Paclitaxel Extends Life in Advanced Pancreatic Cancer

Nick Mulcahy

January 23, 2013

Clinicians may have another therapy option for the patients with difficult-to-treat advanced pancreatic cancer, according to an international study to be presented later this week at the 2013 Gastrointestinal Cancers Symposium in San Francisco, California.

The addition of nanoparticle albumin-bound (nab)-paclitaxel (Abraxane, Celgene) to gemcitabine significantly improved overall survival in treatment-naive patients with metastatic pancreatic cancer, compared with gemcitabine alone.

Specifically, in the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) of 861 patients, overall survival was about 2 months better with the chemotherapy combination than with gemcitabine alone (median, 8.5 vs. 6.7 months; hazard ratio [HR], 0.72; P = .000015).

This is a major improvement.

"While a 2-month improvement may seem modest, in the pancreatic cancer space, this is a major improvement," said Kenneth Yu, MD, from the Memorial Sloan-Kettering Cancer Center in New York City, who was not involved in the study but was asked to comment by Medscape Medical News.

The rate of 1-year survival was better with the chemotherapy combination than with gemcitabine alone (35% vs 22%; P = .0002), as was the rate of 2-year survival (9% vs 4%; P = .02).

Celgene will submit these data in an approval application for the indication of pancreatic cancer in both the United States and Europe during the first half of 2013, and in other countries later this year. Nab-paclitaxel is already marketed for use in metastatic breast cancer.

If nab-paclitaxel is approved in combination with gemcitabine, it will, in a way, maintain a kind of status quo in advanced disease. That's because gemcitabine, alone or in combination with other agents, has been the "reference regimen" for advanced pancreatic cancer for an extended period of time, according to the authors of a study comparing the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) with gemcitabine (N Engl J Med. 2011;364:1817-1825).

That study provided the best survival time ever reported in metastatic pancreatic cancer. Overall survival was better with FOLFIRINOX than with gemcitabine (11.1 vs 6.8 months; P < .0001).

A number of factors influence which drug combination that clinicians will chose in the future.

The New York Times reports that nab-paclitaxel therapy costs around $6000 to $8000 a month, which will likely be more expensive than FOLFIRINOX.

However, toxicity has been a concern with the 4-drug combination, and experts have openly expressed doubt that FOLFIRINOX should become the international standard of care for metastatic pancreatic cancer because of its adverse effects. Researchers have stated that FOLFIRINOX may be best used in patients younger than 76 years who have advanced disease and a good performance status.

Dr. Yu agrees with this assessment. At Memorial Sloan-Kettering, "FOLFIRINOX remains the treatment of choice for our pancreatic cancer patients who are relatively fit," he said. However, he acknowledged the need for "judicious adjustment in dosing" with the regimen.

Most patients are less robust, he explained. In the many patients who are weakened by their cancer, the combination of gemcitabine plus nab-paclitaxel "is a new and effective treatment that we can offer," he said.

The overall survival benefit of the different regimens needs to be balanced with other considerations.

"While the overall survival of patients treated with gemcitabine and nab-paclitaxel does not reach the level seen in patients treated with FOLFIRINOX, the toxicity profile [of gemcitabine plus nab-paclitaxel] does seem better, with only modestly increased levels of neutropenia and fatigue," said Dr. Yu.

MPACT Study Details

In the open-label MPACT, patients were randomly assigned to 1 of 2 regimens: nab-paclitaxel 125 mg/m² followed by gemcitabine 1000 mg/m² for 3 weeks, then a week of rest; or gemcitabine 1000 mg/m² administered weekly for 7 weeks, then a week of rest, followed by cycles of weekly gemcitabine administration for 3 weeks and a week of rest.

The combination demonstrated a statistically significant improvement in key secondary end points, compared with gemcitabine alone.

These improvements include a 31% reduction in the risk for progression or death with the chemotherapy combination, compared with gemcitabine alone (median progression-free survival, 5.5 vs 3.7 months; HR, 0.69; P = 0.000024), and a better overall response rate (23% vs 7%). Median time to treatment failure was also significantly better with the chemotherapy combination (5.1 vs 3.6 months; HR, 0.70; P < 0.0001).

According to company press materials, there were more grade 3/4 treatment-related adverse events with nab-paclitaxel plus gemcitabine than with gemcitabine alone; the most common were neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%). In the nab-paclitaxel plus gemcitabine group, median time to neuropathy improvement was 29 days. There was no difference between the groups in serious life-threatening toxicity (4% in each group).

"The past few decades have brought us very few treatment advances for patients with advanced pancreatic cancer, which is both deadly and incredibly difficult to treat," said Daniel Von Hoff, MD, lead author of MPACT, in a press statement. He is from the University of Arizona College of Medicine in Tucson. "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," he said.

The study was funded by Celgene.

2013 Gastrointestinal Cancers Symposium (GICS): Abstract LBA 148. To be presented January 25, 2013.