The use of cabazitaxel over abiraterone acetate or enzalutamide may continue as a standard of care in men with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and either of those 2 androgen receptor-targeted agents.
Bertrand Tombal, MD, PhD
The use of cabazitaxel (Jevtana) over abiraterone acetate (Zytiga) or enzalutamide (Xtandi) may continue as a standard of care in men with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with docetaxel and either of those 2 androgen receptor (AR)-targeted agents, based on results of a poster presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program.1
Study authors led by Bertrand Tombal, MD, PhD, professor and chairman of urology at the Université catholique de Louvain, Cliniques universitaires Saint-Luc in Brussels, Belgium, determined the robustness of the overall survival benefit observed in the previously published CARD (NCT02485691) trial by using stratified multivariate analysis to explore the effects of baseline characteristics as well as evaluating efficacy from multiple treatment time points in each study arm.1,2
CARD was a multicenter, randomized, open-label study evaluating patients with mCRPC who had progressed within 12 months of receiving an AR-targeted therapy before or after docetaxel.2
Patients were randomized 1:1 to therapy with cabazitaxel (25 mg/m2 every 3 weeks) plus prednisone (10 mg daily) or either control regimen of abiraterone (1000 mg once daily) plus prednisone (5 mg twice daily) or enzalutamide (160 mg once daily), depending on which agent they had previously received. Patients in the cabazitaxel arm also received granulocyte colony-stimulating factor.
Cabazitaxel improved median radiographic progression-free survival by over 4 months (8.0 months with cabazitaxel vs 3.7 months with abiraterone or enzalutamide [HR, 0.54; 95% CI, 0.40-0.73; P <.0001]). Median OS with cabazitaxel was 13.6 months compared with 11.0 months for patients receiving abiraterone or enzalutamide (HR, 0.64; 95% CI, 0.46-0.89; P =.0078).2
In the current analysis, OS was determined from the date of diagnosis of metastatic disease, date of mCRPC diagnosis, and time of initiation of first and second life-extending therapy (LET). Prognostic factors affecting OS were evaluated using univariate analysis and a stepwise multivariate Cox regression analysis.
The investigators identified M1 disease at diagnosis, visceral metastases, Gleason score between 8 to 10 at diagnosis, prior therapy with curative intent, and type of progression as categorical covariates. Continuous covariates included hemoglobin, prostate-specific antigen (PSA), lactate dehydrogenase (LDH) levels, alkaline phosphatase levels, neutrophil-to-lymphocyte ratio, neutrophil count, and testosterone.
Patient baseline characteristics showed median age was 70 years and the majority of patients had metastases to bone: 83.3% in the cabazitaxel arm (n =129) and 88.0% in the abiraterone or enzalutamide arm (n = 126). In the cabazitaxel arm at prior LET, 43.4% received abiraterone and 55.8% received enzalutamide. In the abiraterone and enzalutamide arm, 53.2% received abiraterone and 46.8% received enzalutamide.
When reviewing data from metastatic disease diagnosis, the investigators reported that cabazitaxel conferred a median OS of 54.7 months compared with 42.5 months for either abiraterone or enzalutamide. Reviewing OS from the date of mCRPC diagnosis, patients receiving cabazitaxel had a median OS of 40.9 months compared with 31.3 months for abiraterone or enzalutamide.
Patients who received cabazitaxel were also favored for OS from first and second LET initiation compared with patients who received abiraterone or enzalutamide. Median OS for first LET in the cabazitaxel arm was 36.4 months versus 30.5 months in the abiraterone or enzalutamide arm. Corresponding rates from the second LET initiation showed medians of 24.2 versus 21.9 months.
Table 1. Univariate analysis of OS in CARD Trial1 (Click to Enlarge)
Table 2. Multivariate analysis of OS in CARD Trial1 (Click to Enlarge)
In conclusion, the investigators wrote that the survival benefit of the treatment sequence, docetaxel and one AR-targeted agent followed by cabazitaxel, was consistent for any treatment starting point, which was confirmed by stratified multivariate analysis.
Multivariate analysis revealed that high neutrophil-to-lymphocyte ratio, low hemoglobin level, and high PSA levels were associated with worse OS (Table 2).1
Univariate analysis revealed that higher neutrophil-to-lymphocyte ratio, higher PSA levels, lower hemoglobin values, higher LDH values, higher alkaline phosphatase values, and higher neutrophil count were associated with worse OS (Table 1).1