Sequencing Abiraterone Acetate, Cabazitaxel, and Enzalutamide in Post-Docetaxel mCRPC: Exploiting Efficacy and Avoiding Cross-Resistance
Abiraterone acetate, enzalutamide, and cabazitaxel have been shown to prolong overall survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have progressive disease or have become intolerant to docetaxel, but the optimal sequencing of these agents remains unclear. In an update from a multicenter Italian experience in routine clinical practice, Caffo and colleagues reported their experience with 254 patients with mCRPC who received 2 or 3 of these newer drugs after the patients’ disease progressed while receiving docetaxel (Caffo O, et al. ESMO 2014: Abstract 790P).
Of the 254 patients with mCRPC, bone, nodal, or visceral metastases were present in 89%, 56%, or 20%, respectively. The patients received abiraterone acetate, enzalutamide, or cabazitaxel second-, third-, or fourth-line therapy in various sequences, all after receiving docetaxel.
The Table details the biochemical response rate (BRR)—comprised on a prostate-specific antigen decline ?50%—the overall response rate (ORR), and the median progression-free survival (PFS) of each treatment sequence.
As shown in the Table, the best BRR and ORR responses were noted in the groups receiving abiraterone acetate or enzalutamide as third-line therapy after cabazitaxel, and when cabazitaxel followed abiraterone acetate, but were not as robust when enzalutamide followed abiraterone acetate or abiraterone acetate followed enzalutamide, although the longest PFS was noted in patients sequencing the androgen antagonists.
A limited number of patients received the sequences shown in the Table as fourth-line therapy, and similarly, the best results were observed when cabazitaxel was followed by abiraterone acetate or enzalutamide, or when abiraterone acetate or enzalutamide was followed by cabazitaxel, but not when the 2 androgen inhibitors were sequenced.
Although this is a retrospective study, the data represent actual clinical practice and begin to provide some insight into reasonable sequencing approaches with cabazitaxel, abiraterone acetate, and enzalutamide in the post-docetaxel setting. However, no safety data were presented in this study, especially in the groups receiving a second chemotherapy drug (cabazitaxel) immediately after docetaxel, which is known to cause treatment-related adverse events in these patients (Wissing MD, et al. Int J Cancer. 2014;Sep 20 [Epub ahead of print]).