Cabazitaxel vs docetaxel in chemotherapy-naive (CN) patients with metastatic castration-resistant prostate cancer (mCRPC): A three-arm phase III study (FIRSTANA)

Background: The Phase III TROPIC study (NCT00417079 ) reported significant improvement in overall survival (OS) for cabazitaxel 25 mg/m2IV Q3W plus prednisone 10 mg PO QD (P) vs. mitoxantrone plus P in mCRPC pts previously treated with a docetaxel (D)‐containing regimen. The FIRSTANA study examined if cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) IV Q3W plus P is superior to docetaxel 75 mg/m2 (D75) IV Q3W plus P in terms of OS in CN mCRPC pts. Methods: In this multinational, open label phase III study, mCRPC pts, ECOG PS 0‐2, who had progressed after castration were randomized 1:1:1 to C20, C25 or D75 IV Q3W plus P. The primary endpoint was OS. Key secondary endpoints were safety, progression free survival (PFS), tumor PFS, tumor response (RECIST 1.1), PSA response, PSA PFS, pain response, pain PFS, time to skeletal‐related events (SRE) and health‐related quality of life (HRQOL). Results: Between May 2011 and April 2013, 1168 pts were randomized (C20=391, C25=389, D75=388). Baseline demographics and disease characteristics were similar across cohorts. The median number of treatment cycles was 9 for all dose groups. In the ITT analysis, median OS was 24.5 months for C20, 25.2 months for C25 and 24.3 months for D75. HR for C20 vs. D75 was 1.009 (0.85 to 1.197, p=0.9967) and for C25 vs. D75 was 0.97 (0.819 to 1.16, p=0.7574), indicating that C20 and C25 were not superior to D75 in terms of OS. PFS was 4.4 months for C20, 5.1 months for C25 and 5.3 months for D75 (NS). Tumor responses were superior in C25 (41.6%) compared to D75 (30.9%), p=0.0370. Other secondary endpoints did not significantly differ across dose groups. Adverse events (AEs) grade 3‐4 were 41.2% in C20, 60.1% in C25 and 46.0% in D75; pts discontinuing treatment due to an AE were 25.2% in C20, 31.7% in C25 and 33.9% in D75. Febrile neutropenia, diarrhea and hematuria were more frequent in C25; peripheral neuropathy, peripheral edema, alopecia and nail disorders were more frequent in D75. Conclusions: C20 and C25 did not demonstrate superiority for OS compared to D75 in CN mCRPC pts. Among secondary endpoints only tumor responses were significantly superior for C25. AEs were less frequent in C20 for most categories.