DS_10.1177_2381468318781811 – Supplemental material for The Lifetime Health Burden of Delayed Graft Function in Kidney Transplant Recipients in the United States

<p>Supplemental material, DS_10.1177_2381468318781811 for The Lifetime Health Burden of Delayed Graft Function in Kidney Transplant Recipients in the United States by Devin Incerti, Nicholas Summers, Thanh G. N. Ton, Audra Boscoe, Anil Chandraker and Warren Stevens in MDM Policy & Practice</p

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

<div><p>Background</p><p>The 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.</p><p>Methods</p><p>A 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.</p><p>Results</p><p>Three 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.</p><p>Conclusions</p><p>The 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.</p></div

Hazard ratios (HR) and 95% Confidence Interval (CI) for progression-free survival (PFS) for studies included in the indirect treatment comparison for cabazitaxel, abiraterone acetate and enzalutamide.

<p>Hazard ratios (HR) and 95% Confidence Interval (CI) for progression-free survival (PFS) for studies included in the indirect treatment comparison for cabazitaxel, abiraterone acetate and enzalutamide.</p

Odds ratios and 95% Credible Intervals for grade 3 and above adverse events.

<p>Odds ratios and 95% Credible Intervals for grade 3 and above adverse events.</p

Hazard ratios and 95% Credible Intervals for indirect treatment comparisons between cabazitaxel, abiraterone and enzalutamide using Bayesian fixed and random effects and Frequentist fixed effects modeling.

<p>Hazard ratios and 95% Credible Intervals for indirect treatment comparisons between cabazitaxel, abiraterone and enzalutamide using Bayesian fixed and random effects and Frequentist fixed effects modeling.</p

Comparison of age, ECOG score, and lengths of follow-up for overall survival (OS) and progression-free survival (PFS) for clinical trials used in the indirect treatment comparison.

<p>Comparison of age, ECOG score, and lengths of follow-up for overall survival (OS) and progression-free survival (PFS) for clinical trials used in the indirect treatment comparison.</p

Baseline characteristics of the studies included in the indirect treatment comparison for cabazitaxel, abiraterone acetate and enzalutamide.

<p>Baseline characteristics of the studies included in the indirect treatment comparison for cabazitaxel, abiraterone acetate and enzalutamide.</p

Median overall survival and progression-free survival hazard ratios (HRs) and 95% Credible Intervals for cabazitaxel, abiraterone and enzalutamide using Bayesian fixed effects modeling.

<p>Median overall survival and progression-free survival hazard ratios (HRs) and 95% Credible Intervals for cabazitaxel, abiraterone and enzalutamide using Bayesian fixed effects modeling.</p

Hazard ratios (HR) and 95% Confidence Interval (CI) for overall survival (OS) for studies included in the indirect treatment comparison for cabazitaxel, abiraterone acetate and enzalutamide.

<p>Hazard ratios (HR) and 95% Confidence Interval (CI) for overall survival (OS) for studies included in the indirect treatment comparison for cabazitaxel, abiraterone acetate and enzalutamide.</p

Percent grade 3 and above adverse events (AEs) for cabazitaxel, abiraterone acetate and enzalutamide and their comparators.

<p>Percent grade 3 and above adverse events (AEs) for cabazitaxel, abiraterone acetate and enzalutamide and their comparators.</p