The albumin-bound formulation of paclitaxel has been approved by the Food and Drug Administration as a first-line treatment for metastatic adenocarcinoma of the pancreas, in combination with gemcitabine, the agency announced on Sept. 6.
The expanded indication for Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound), a microtubule inhibitor, is based on a study that found survival and progression-free survival were a median of almost 2 months longer among those treated with Abraxane and gemcitabine, compared with those treated with gemcitabine alone, according to the FDA statement announcing the approval.
When pancreatic cancer is diagnosed in an advanced stage and is inoperable, which is often when pancreatic cancer is diagnosed, "and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The international study compared Abraxane plus gemcitabine with gemcitabine alone as a first-line treatment in 861 people with metastatic adenocarcinoma of the pancreas. Their median age was 63 years, and almost half had three or more sites of metastasis (84% had liver metastases).
Median overall survival was 8.5 months in those on the combination vs. 6.7 months among those on gemcitabine alone, a highly statistically significant difference. Median progression-free survival was 5.5 months among those on the combination vs. 3.7 months for those on gemcitabine alone, also a highly statistically significant difference. In addition, 23% of those in the combination arm had a confirmed complete or partial overall response, compared with 7% of those on gemcitabine, according to the prescribing information.
The results of the study, IMPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), have been submitted for publication, according to the Celgene statement announcing the approval, and were presented at the American Society of Clinical Oncology annual meeting this year.
Common adverse events associated with treatment with Abraxane and gemcitabine included neutropenia, thrombocytopenia, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, fever, vomiting, rash, and dehydration. Fever, dehydration, pneumonia, and vomiting were the most common serious adverse events. Other "clinically important" adverse events included sepsis and pneumonitis, according to the FDA.
According to the new prescribing information, for pancreatic cancer, Abraxane (125 mg/m2) is administered intravenously on days 1, 8, and 15 of each 28-day cycle, followed by gemcitabine immediately afterwards. In the United States, pancreatic cancer is the fourth-leading cause of cancer deaths, according to the FDA statement, which cites National Cancer Institute estimates that 45,220 patients will be diagnosed with pancreatic cancer and 38,460 will die from the disease in 2013.
Abraxane, marketed by Celgene, was approved for treating breast cancer in 2005 and non–small cell lung cancer in 2012. Gemcitabine, a nucleoside metabolic inhibitor marketed as Gemzar by Eli Lilly, was approved in 1996 and is also available in generic formulations. Gemcitabine is approved as a single agent to treat pancreatic cancer.
The revised label is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf.