The first-ever presentation of phase III data from the investigational taxane cabazitaxel showed a 30% improvement in survival in men with metastatic castration-resistant prostate cancer.
San Francisco-The first-ever presentation of phase III data from the investigational taxane cabazitaxel showed a 30% improvement in survival in men with metastatic castration-resistant prostate cancer, researchers reported at the 2010 Genitourinary Cancers Symposium here.
The new agent recently received fast track designation from the FDA, and the rolling submission has already started.
Men in the cabazitaxel group had a median overall survival of 15.1 months versus 12.7 months for the mitoxantrone group, a hazard ratio of 0.70 (p<.0001).
The overall survival benefit was consistent across all subgroups in the study population. Progression-free survival, a composite of tumor, PSA, and pain assessment, was also statistically significant at 2.8 months for cabazitaxel versus 1.4 months for mitoxantrone, a hazard ratio of 0.74 (p<.0001).
"This is a very difficult-to-treat patient population," Dr. Sartor told Urology Times. "Cabazitaxel is the first successful chemotherapy treatment to appear since Taxotere was approved. I would anticipate that it would be approved fairly rapidly, and uptake should be even faster."
"The survival data were what really impressed me," Dr. Sandler said. "This is an improved docetaxel with results so strong it will undoubtedly be tried as first-line therapy for prostate cancer and in other cancers as well."
The new drug is a semi-synthetic taxane designed to overcome resistance to docetaxel. Prostate cancers develop resistance to docetaxel by way of the multidrug resistant (MDR) pump, which pumps chemotherapeutic agents out of the cell before the drug can act. Cabazitaxel appears to evade the MDR pump, which allows the drug to remain in cancer cells and kill them. Preclinical data showed that cabazitaxel is as potent as docetaxel against sensitive cells and cancer lines and has activity against tumor cells and models that are resistant to or not sensitive to existing taxane agents, including docetaxel.
'Significant' neutropenia seen
Phase I trials showed clinical activity against docetaxel-resistant disease, but also showed significant neutropenia. TROPIC data confirm both of those findings. The most frequent grade 3/4 toxicity was neutropenia, seen in 81.7% of cabazitaxel patients versus 58% of mitoxantrone patients. Febrile neutropenia was seen in 7.5% of cabazitaxel patients versus 1.3% of mitoxantrone patients. Other common adverse events included diarrhea, fatigue, nausea, vomiting, asthenia, hematuria, and abdominal pain. Deaths due to adverse events were 4.9% in the cabazitaxel arm and 1.9% in the mitoxantrone arm.
Toxicity-related deaths varied widely across study centers.
"Neutropenia is something that needs to be monitored carefully," Dr. Sartor said. "There was a high adverse event rate related to neutropenia, but these patients were sicker and more heavily pretreated than in most trials. A number of men had already undergone up to three different chemotherapy regimens. Cabazitaxel represents a significant new option for these patients who are difficult to treat."
Dr. Sartor and co-authors of this study disclosed financial interest or other relationship with sanofi-aventis, the manufacturer of cabazitaxel. Dr. Sandler disclosed that he is a consultant/adviser for sanofi-aventis.