June 18, 2010 (UPDATED June 22, 2010) — Cabazitaxel (Jevtana, Sanofi-Aventis) has been approved in the United States for second-line use in advanced hormone-refractory prostate cancer in men who have already been treated with docetaxel.
Cabazitaxel is the first chemotherapy to have shown a survival benefit in this setting since docetaxel. It was described as "clearly a major advance in secondary chemotherapy for advanced prostate cancer" by Nicholas J. Vogelzang, MD, from US Oncology in Woodlands, Texas, at the recent American Society of Clinical Oncology 2010 Annual Meeting, as reported by Medscape Oncology.
The drug was approved ahead of schedule by the US Food and Drug Administration (FDA). It was reviewed under the agency's priority review program, an expedited 6-month review for drugs that offer an advance in treatment or provide a treatment where none exists. Under this program, a decision was expected before September 30; in fact, it was made in 11 weeks.
"Patients have few therapeutic options in this disease setting," said Richard Pazdur, MD, director of the Office of Oncology Drug Products at the FDA.
"This is truly a significant announcement for the prostate cancer community, addressing an unmet medical need," noted Oliver Sartor, MD, Plitz Professor of Cancer Research at Tulane Medical School in New Orleans, Louisiana, in a statement. Dr Sartor was the lead investigator in the drug’s pivotal trial, known as TROPIC.
Survival Benefit in TROPIC Trial
The approval was based on data from the single company-sponsored phase 3 TROPIC clinical trial, conducted in 755 patients. All patients had advanced hormone-refractory prostate cancer and all had previously been treated with docetaxel. They were randomized to receive either cabazitaxel or mitoxantrone, both in combination with prednisone.
The median overall survival was 15.1 months with cabazitaxel and 12.7 months with mitoxantrone (hazard ratio, 0.72; 95% confidence interval, 0.61 - 0.84; P < .0001).
Investigator-assessed tumor response rates using Response Evaluation Criteria in Solid Tumors were 14.4% for the cabazitaxel group vs 4.4% for the mitoxantrone group (P = .0005), although no complete responses were observed in either treatment group.
The manufacturer, Sanofi-Aventis, noted in a press release that the most common adverse reactions (grades 1 to 4), seen in 10% or more of patients, were neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysguesia, cough, arthralgia, and alopecia. The most common adverse events leading to discontinuation of the drug were neutropenia and renal failure. In the cabazitaxel group, 18% of patients discontinued because of adverse events, compared with 8% in the mitoxantrone group.
The company also warns that neutropenic deaths have been reported. To monitor the occurrence of neutropenia, frequent blood cell counts should be performed, and cabazitaxel should not be given to patients with neutrophil counts of 1500 cells/mm3 or less. Primary prophylaxis with granulocyte colony-stimulating factor should be considered in patients with high-risk clinical features.
Concern about the toxicity of the drug was raised recently by Ian Tannock, MD, PhD, from the University of Toronto in Ontario. In a recent interview with Medscape Oncology, he said that "by far the most worrying toxicity is residual neuropathy," although he noted that many patients will have experienced fatigue and neuropathy while on docetaxel.
Medscape Medical News © 2010 Medscape, LLC
Send press releases and comments to email@example.com.
Cite this: Cabazitaxel: New Chemo Approved for Advanced Prostate Cancer - Medscape - Jun 18, 2010.