FDA Approval for Cabazitaxel
- Approved for use in combination with prednisone for treatment of metastatic hormone refractory prostate cancer previously treated with a docetaxel-containing regimen.
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On June 17, 2010, the U.S. Food and Drug Administration (FDA) approved cabazitaxel (Jevtana® Injection, made by Sanofi-Aventis) for use in combination with prednisone for treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen.
The approval is based primarily on the results of a randomized, open-label, international trial of 755 patients with mHRPC previously treated with docetaxel-containing regimens. Patients were randomly assigned to receive either cabazitaxel 25 mg/m2 intravenously every three weeks in combination with prednisone 10 mg/day or mitoxantrone 12 mg/m2 intravenously every three weeks in combination with prednisone 10 mg/day. Patients were treated until disease progression, death, unacceptable toxicity, or completion of 10 cycles of therapy.
Median survival was 15.1 months for patients treated with cabazitaxel and 12.7 months for patients treated with mitoxantrone [HR 0.70 (95 percent CI 0.59-0.83), p<0.0001.] Investigator-assessed response rates using RECIST criteria were 14.4 for cabazitaxel-treated patients and 4.4 percent for mitoxantrone-treated patients, p=0.0005. No complete responses were observed in either group of patients.
The most common grade 1-4 adverse reactions included neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia and alopecia. The most common grade 3-4 adverse reactions were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue and asthenia.
Deaths due to causes other than disease progression within 30 days of the last dose were reported in 18 (5 percent) cabazitaxel-treated patients and 3 (<1 percent) mitoxantrone-treated patients. The most common fatal adverse reactions in cabazitaxel-treated patients were infections and renal failure. One death was due to diarrhea-induced dehydration and electrolyte imbalance.
G-CSF may be administered to reduce the risks of neutropenic complications associated with cabazitaxel use. Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features including patients who are 65 years or older, have poor performance status, had previous episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other serious comorbidities. Therapeutic use of G-CSF and secondary prophylaxis should be considered in patients at an increased risk for neutropenia complications.
Because of the risk of severe hypersensitivity, patients should be premedicated with an antihistamine, a corticosteroid and an H2 antagonist. In addition, antiemetic prophylaxis is recommended.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.