CHICAGO—Cabazitaxel is the first treatment to show a survival benefit in patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from a phase 3 trial.
On June 17, cabazitaxel became the first drug approved by the US Food and Drug Administration (FDA) for the treatment of hormone-refractory prostate cancer. Results from the phase 3 trial delivered at ASCO were included in the FDA review.
“The standard of care for treating mCRPC is docetaxel, which improves both overall survival and quality of life. At progression following docetaxel, however, there is currently no standard of care for treating these patients, although there are a number of investigational drugs being studied, and treatment in this setting is largely for palliation,” said Johann Sebastian De Bono, MD, PhD, who presented the final and updated results of the multinational trial.
Cabazitaxel is a tubulin-binding drug developed specifically to overcome the emergence of resistance to established taxanes, including docetaxel.
For this multinational trial, conducted in 146 centers in 26 countries, 755 patients with mCRPC were randomized to receive either prednisone (10 mg/day) in combination with either mitoxantrone (12 mg/m2) or cabazitaxel (25 mg/m2) administered three times weekly. Patients enrolled had received prior hormone therapy, chemotherapy, and radiotherapy, but had progressive disease during or after treatment with docetaxel (cumulative dose ≥225 mg/m2).
Upon primary intent-to-treat analysis, overall survival in the cabazitaxel combination arm was significantly higher compared with that in the mitoxantrone arm (15.1 months vs 12.7 months, respectively; P <.0001). Recently updated results of overall survival showed that the combination of cabazitaxel and prednisone significantly reduced the risk of death by 28% (P <.0001).
Pain-free survival, response rates, and time to progression also significantly favored the cabazitaxel arm.
“The safety profile of this drug was manageable, but proactive management of side effects associated with this drug, particularly febrile neutropenia and diarrhea, has to be carefully considered when treating a patient with this drug,” said De Bono, senior lecturer at Royal Marsden Hospital, London.
The most frequent grade 3/4 hematologic adverse events in the cabazitaxel arm were neutropenia (81.7%), leukopenia (69.2%), anemia (10.5%), and febrile neutropenia (7.5%). Discontinuation of treatment due to adverse events occurred in 18.3% of patients in the cabazitaxel arm, and 8.4% of those in the mitoxantrone arm.
Deaths due to adverse events were 4.9% in the cabazitaxel arm (predominantly caused by neutropenia and its complications) versus 1.9% in the mitoxantrone arm.
“Cabazitaxel demonstrates a statistically and clinically significant improvement in overall survival—evident across all subgroups—compared with mitoxantrone in this study population.
Cabazitaxel also improved secondary end points of progression-free survival, response rate, and time to progression,” he concluded.