1: Efficacy of cabazitaxel as first-line therapy and lower dose cabazitaxel for men with mCRPC
The TROPIC trial (published in 2010) demonstrated that 25 mg/m2 cabazitaxel offered superior overall survival (OS) compared to mitoxantrone (median OS 15.1 vs 12.7 months; p<0.001) and it is currently recommended as second-line treatment for men with metastatic castrate resistant prostate cancer (mCRPC) previously treated with docetaxel. Two phase III trials published in the Journal of Clinical Oncology this month address whether cabazitaxel can be used as first-line treatment and if it is effective at a lower dose.
FIRSTANA assigned 1,168 men with chemotherapy-naïve mCRPC to first-line treatment with either cabazitaxel 20 mg/m2 (C20), cabazitaxel 25 mg/m2 (C25) or docetaxel 75 mg/m2 (D75). Although the trial was not powered to prove non-inferiority, there were no significant differences between progression free survival or OS with median OS of 24.5 months for C20, 25.2 months for C25 and 24.3 months for D75 arms. 41.2%, 60.1% and 46.0% of men in the C20, C25 and D75 arms respectively, experienced grade 3 or 4 adverse effects, with febrile neutropenia, diarrhea and hematuria more frequently seen in men in the C25 arm and peripheral neuropathy, peripheral edema and alopecia more frequent in D75.
The PROSELICA trial, involving 1,200 patients, looked more closely into the efficacy of low dose cabazitaxel (20 mg/m2) (C20) compared to standard of care, 25 mg/m2 cabazitaxel (C25), for men with mCRPC post-docetaxel. C20 was shown to be non-inferior compared to C25 (median OS 13.4 vs 14.5 months; HR 1.024) and was also better tolerated with 39.7% of C20 patients having grade 3 or 4 adverse events compared to 54.5% of C25 patients.
Taken together, these studies demonstrate that cabazitaxel could be considered as a first-line chemotherapy option for patients who are contraindicated for docetaxel (i.e. those intolerant of docetaxel or who have baseline peripheral neuropathy). In addition, as lower dose cabazitaxel caused fewer toxicities this may be an option for patients who are frail or at high risk for febrile neutropenia and may not tolerate higher doses of cabazitaxel.