Prognostic Factors for Sequencing Abiraterone, Cabazitaxel, and Enzalutamide in the Post-Docetaxel Setting
Abiraterone, enzalutamide, and cabazitaxel have been shown in recent studies to prolong overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have progressive disease or have become intolerant to docetaxel. However, the optimal sequencing of these agents is still a matter of controversy. In a large, retrospective cohort study presented by Oudard and colleagues, the impact of prognostic factors and sequencing of abiraterone, enzalutamide, and cabazitaxel on OS was evaluated (Oudard S, et al. ESMO 2014: Abstract 789P).
In this multicenter study, records of 246 patients with mCRPC were examined for selected clinical variables (disease history, clinical characteristics, and outcomes) and whether they had received cabazitaxel or abiraterone/enzalutamide post-docetaxel. At initiation of the first therapy post-docetaxel, 86% of the patients had ECOG status 0-1, 61% had pain, 63% had radiologic progression of disease, and 47% had clinical disease progression, with 17% having visceral metastases. Although all patients eventually received cabazitaxel after failing docetaxel therapy, abiraterone or enzalutamide was given before cabazitaxel in 25% of the patients or after cabazitaxel in 18% of patients.
The median OS was 13.5 months when cabazitaxel was used without abiraterone or enzalutamide, 28.9 months if patients received abiraterone or enzalutamide after cabazitaxel, and 22.4 months if abiraterone or enzalutamide was administered before cabazitaxel.
The OS duration was significantly reduced in all the groups in patients with visceral metastases and in those with pain at initiation of first therapy after docetaxel. Conversely, the OS duration was significantly prolonged in patients who received 2 active therapies post-docetaxel failure, with a greater OS benefit observed when abiraterone or enzalutamide was given after cabazitaxel instead of before cabazitaxel. Oudard and colleagues concluded that these patients derived the greatest OS benefit from a treatment sequence of docetaxel followed by cabazitaxel followed by abiraterone or enzalutamide.
There are significant limitations to these results, however, including the retrospective design of the study, and the lack of accounting for serious treatment-related adverse events associated with the use of a treatment sequence of 2 chemotherapy agents in a row. Moreover, no statistical analysis was conducted to compare the sequences of cabazitaxel followed by abiraterone or of enzalutamide versus abiraterone or enzalutamide followed by cabazitaxel, leaving open the question which sequencing option is optimal for these patients.