Evidence for Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer

Strongest Evidence: The CARD Trial

The National Comprehensive Cancer Network recommends cabazitaxel as a Category 1 preferred option after progression on docetaxel and a novel hormone therapy, demonstrating superior outcomes compared to switching to enzalutamide in this heavily pretreated population, with a median overall survival of 13.6 months versus 11.0 months with switching to abiraterone/enzalutamide (HR 0.64, p=0.008) 1
Cabazitaxel improved radiographic progression-free survival to 8.0 months versus 3.7 months with the alternative hormone therapy (HR 0.54, p<0.0001) in patients who had progressed on both docetaxel and one novel hormone therapy 1

The NCCN 2023 guidelines designate cabazitaxel as a Category 1 preferred option specifically after progression on docetaxel and a novel hormone therapy, with a recommended dose of 20 mg/m² every 3 weeks for fit patients, with or without growth factor support 1
The American Urological Association 2013 guidelines support the use of cabazitaxel or enzalutamide for patients with good performance status who received abiraterone prior to docetaxel 2

Primary prophylaxis with G-CSF is essential given the high risk of neutropenic complications in this heavily pretreated population, with 92% of CARD trial patients receiving primary G-CSF prophylaxis 1
Premedication before each infusion, including antihistamines, H2 antagonists, and corticosteroids, is necessary to prevent hypersensitivity reactions 1

Grade 3-4 adverse events occur in 39.7-56.3% of patients, but are manageable with appropriate prophylaxis, with neutropenia being the primary toxicity (grade 3-4 neutropenia occurs in 41.8-73.3% depending on dose) 1
Febrile neutropenia occurs in 7-9% of patients, with a toxic death rate of 4.9% primarily from sepsis and renal failure 1

The American Urological Association recommends against initiating cabazitaxel in patients with poor performance status (ECOG ≥3) where toxicity risk outweighs benefit 2

The National Comprehensive Cancer Network (NCCN) guidelines recommend that cabazitaxel should not be initiated in patients with severe hepatic impairment, as it is contraindicated in such cases 3, 4
Cabazitaxel is specifically indicated for metastatic castration-resistant prostate cancer (mCRPC) that has progressed after treatment with a docetaxel-containing regimen, according to the NCCN guidelines 3, 4

The NCCN guidelines recommend cabazitaxel as a preferred option (category 1) specifically after progression on docetaxel in patients with mCRPC 4
The NCCN guidelines do not recommend cabazitaxel in docetaxel-naïve patients, despite the FIRSTANA study showing activity in chemotherapy-naïve patients 4

Daily prednisone or prednisolone must be prescribed and taken throughout cabazitaxel treatment, according to the NCCN guidelines 3, 4
Premedication to prevent hypersensitivity reactions, including antihistamines, H2 antagonists, and corticosteroids, is required before each infusion 3, 4
Antiemetic prophylaxis is also required before each infusion 3, 4
G-CSF (granulocyte colony-stimulating factor) should be considered for prophylaxis, particularly in this heavily pretreated, high-risk population 3, 4

The NCCN guidelines specifically recommend following current guidelines for prophylactic white blood cell growth factor use 3, 4
Growth factors should be started 24-72 hours after completion of chemotherapy and continued through post-nadir recovery, but not administered on the same day as chemotherapy 5