ABRAXANE IMPROVES SURVIVAL IN PANCREATIC CANCER

In September, the US Food and Drug (FDA) approved, for the first time in nearly 8 years, a new treatment for metastatic pancreatic cancer.

Clinicians can now review the details of the clinical trial that was the basis for the FDA approval of nanoparticle albumin-bound (nab)-paclitaxel (Abraxane, Celgene). The study waspublished online October 17 in the New England Journal of Medicine.

The drug was specifically approved for adenocarcinoma of the pancreas, a subtype that accounts for about 95% of cancers of the pancreas.

In the pivotal clinical trial, known as the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), median overall survival was about 2 months better with nab-paclitaxel plus gemcitabine than with gemcitabine alone (8.5 vs 6.7 months; hazard ratio [HR], 0.72; P < .0001).

"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 lead author Daniel Von Hoff, MD, in a press statement when the study was first presented at the 2013 Gastrointestinal Cancers Symposium. He is from the University of Arizona College of Medicine in Tucson.

"While a 2-month improvement may seem modest, in the pancreatic cancer space, this is a major improvement," said Kenneth Yu, MD, at that time. He is from the Memorial Sloan-Kettering Cancer Center in New York City, and was not involved in the study.

In MPACT, the rate of 1-year survival was also better with the combination than with monotherapy (35% vs 22%; P = .0002), as was the rate of 2-year survival (9% vs 4%; P = .02).

In the 861 chemotherapy-naïve patients with metastatic pancreatic cancer, median progression-free survival was better with the combination than with monotherapy (5.5 vs 3.7 months; HR, 0.69; P < .001). The overall response rate was also better with the combination (23% vs 7%; P < .001).

The level of adverse events in the study was acceptable.

Table. Common Adverse Events

Adverse Event	Nab-Paclitaxel Plus Gemcitabine Combination, %	Gemcitabine Monotherapy, %
Febrile neutropenia	3	1
Grade 3 or higher
Neutropenia	38	27
Fatigue	17	7
Neuropathy	17	1

In the combination group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days.

Dr. Von Hoff and his coauthors conclude that "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."

The addition of nab-paclitaxel to the treatment options in this setting has been welcomed by clinicians. As a combination therapy with gemcitabine, it now rivals 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX).

An earlier study comparing FOLFIRINOX with gemcitabine (N Engl J Med. 2011;364:1817-1825) showed that the 4-drug combination provided the best survival time ever reported in metastatic pancreatic cancer. Overall survival was significantly better with FOLFIRINOX than with gemcitabine (11.1 vs 6.8 months; P < .0001).

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

The New York Times reported 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 expressed doubtthat FOLFIRINOX will become the international standard of care for metastatic pancreatic cancer because of its adverse effects. Researchers have stated that FOLFIRINOX might be best used in patients younger than 76 years who have advanced disease and a good performance status.

In less-robust patients, the combination of gemcitabine plus nab-paclitaxel "is a new and effective treatment that we can offer," Dr. Yu said earlier this year.

The study was funded by Celgene. Some of the study authors have financial ties to Celgene, as detailed in the paper.

N Engl J Med. Published online October 16, 2013. Abstract