Cabazitaxel is the first treatment to be licensed for the treatment of metastatic HRPC that has progressed during or after treatment with docetaxel.

Although there is currently no standard treatment for patients with metastatic HRPC who progress following docetaxel, palliative options currently used include mitoxantrone with or without steroids, and a variety of chemotherapy regimens such as 5-fluorouracil, cyclophosphamide and carboplatin/etoposide (these are considered to be the relevant comparators in the NICE final scope for its guidance on cabazitaxel).  None of these interventions has been shown to improve survival in this setting.

The TROPIC study demonstrated that the use of cabazitaxel in the treatment of men with HRPC that had progressed during or following docetaxel therapy was associated with an improvement of 2.4 months in median OS, when compared to mitoxantrone (both in combination with prednisone/prednisolone).  Subgroup analyses found that there was no difference in OS between treatments in those patients who had received 3 cycles or less of docetaxel (<225mg/m2; this was a small subgroup of 59 patients).  Mitoxantrone can be considered as an appropriate choice for an active comparator.

Neutropenia is the most frequently observed adverse reaction of cabazitaxel, and was the most common cause of early death in the TOPIC study.  The dose should be reduced in those with prolonged neutropenia and the next dose should not be given unless the neutrophil count is ≥1,500/mm3. Although dose reductions to 20mg/m2 decrease myelotoxicity, the impact of this reduction on efficacy is unknown and needs to be investigated in further research.  In addition, although the main toxicities (neutropenia and diarrhoea) are manageable if carefully monitored during treatment, they may have an impact on patients with advanced disease who may have been heavily pre-treated with docetaxel (6).  Comparative quality of life data for patients taking cabazitaxel in this setting are awaited.