Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen

Abstract

BackgroundThe objective of this study was to conduct an indirect treatment comparison between cabazitaxel, abiraterone and enzalutamide to determine the clinical efficacy and safety of cabazitaxel relative to comparators in the treatment of patients with metastatic castrate-resistant prostate cancer who progress on docetaxel-based therapies.MethodsA systematic literature review was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm of best supportive care were included in the analysis. Overall survival, progression-free survival, and adverse events were compared within both Bayesian and Frequentist frameworks. The ratios for survival outcomes were estimated using hazard ratios (HR), and the ratios for adverse events between groups were estimated using odds ratios (ORs); uncertainty was reported as 95% confidence (Frequentist) and credible (Baysesian) Intervals.ResultsThree of thirteen trials identified for abstraction were relevant for analyses. Median overall survival was not statistically significantly different for abiraterone (HR = 1.04; 95% CI = 0.83–1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69–1.11) when compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI = 1.01–10.44), diarrhoea (OR = 16.60; 95% CI = 1.41–75.31) and haematuria (OR = 3.88; 95% CI = 1.03–10.09) were more likely to occur in the cabazitaxel group than the abiraterone group, while pyrexia risk was higher in cabazitaxel compared to enzalutamide (OR = 36.23; 95% CI = 1.14–206.40). Frequentist analyses produced similar results.ConclusionsThe scarcity of clinical studies and lack of a common comparator limited analyses. The adverse event results must be interpreted with caution as many were based on small numbers. The results from this analysis indicate comparable survival outcomes and adverse event profiles. As these pivotal studies may not reflect the contemporary treatment landscape and patient profiles, additional research, including head-to-head clinical trials and real world observational studies, should be conducted to further elucidate the beneficial effects of these therapies.

Efficacy and safety of abiraterone acetate plus prednisone vs. cabazitaxel as a subsequent treatment after first-line docetaxel in metastatic castration-resistant prostate cancer: results from a prospective observational study (CAPRO)

“…Thus, in contrast to the crude analysis, our post-hoc Cox proportional-hazards regression analyses found no difference between abiraterone acetate plus prednisone and cabazitaxel plus prednisone in any of the time-to-event outcomes, including overall survival. These latter results are consistent with a recent meta-analysis that indirectly compared three therapies for mCRPC after docetaxel chemotherapy (abiraterone plus prednisone, enzalutamide and cabazitaxel), concluding that there was no significant differences in terms of OS favoring any of the treatments [19].…”

Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel

“…This refractory character of CRPC toward docetaxel chemotherapy has mobilized research efforts to identify new therapeutic options. Abiraterone acetate (an inhibitor of androgen biosynthesis) [ 12 ], enzalutamide (a new generation of antiandrogen) [ 13 ], and cabazitaxel (a new generation of taxotere) [ 14 ] are three relevant examples of new drugs obtained from these research efforts that significantly impacted the median survival of CRPC patients [ 15 , 16 ]. However, resistance again occurs, even for those new drugs, leaving these resistant patients with no viable therapeutic options [ 17 , 18 ].…”

Comparison of Systemic Treatments for Metastatic Castration-Resistant Prostate Cancer After Docetaxel Failure: A Systematic Review and Network Meta-analysis

“…Compared to the previous review ( Fryzek et al, 2018 ), our study provides several novel findings. First, radium-223 was included in the network analysis.…”

“…Consistently, radium-223 showed improved survival compared to BSC and similar efficacy with abiraterone and enzalutamide in this setting. Second, the prior indirect analysis used PFS as one of the efficacy outcomes, while the definitions of PFS were different cross trials ( Fryzek et al, 2018 ). In this study, we compared the bPFS outcomes, which were measured more consistently in the included trials.…”

“…As such, the current guidelines do not recommend one treatment over the others ( Cornford et al, 2021 ; J Natl Compr Canc Netw, 2021 ). One preliminary analysis has attempted to compare these active treatments indirectly but was limited by a few number of included studies and the exclusion of radium-223 ( Fryzek et al, 2018 ). In addition, the costs and treatment courses of these drugs vary widely ( Pollard et al, 2017 ).…”