Real-World Effectiveness of Sipuleucel-T on Overall Survival in Men with Advanced Prostate Cancer Treated with Androgen Receptor-Targeting Agents

Abstract

Introduction: The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) continues to evolve. Sipuleucel-T was the first immunotherapy approved by the US Food and Drug Administration (FDA) to treat asymptomatic or minimally symptomatic mCRPC. The androgen receptor-targeting agents (ARTAs) abiraterone acetate and enzalutamide were initially approved to treat mCRPC. Looking at chemotherapy-naïve men with mCRPC, we compared survival outcomes between the sipuleucel-T + ARTA cohort (men who received either sipuleucel-T or an ARTA in the first line, and then the other in the second line within 6 months) and the ARTA monotherapy cohort (men who only received ARTA monotherapy).

Methods: This retrospective cohort analysis used longitudinal, adjudicated claims data from the US Medicare Fee-for-Service 100% research identifiable dataset that includes both urologic and oncologic practice settings. Eligible men started their first mCRPC treatment with either sipuleucel-T or ARTA in either 2014 or 2015 and had continuous Medicare Parts A, B, and D eligibility for the subsequent 3 years. A multivariable Cox proportional hazards regression model was used to analyze overall survival (OS), both overall and by index year, and to control for differences.

Results: The sipuleucel-T + ARTA and ARTA monotherapy cohorts comprised 773 and 4642 men, respectively, with different characteristics at treatment start. The most commonly used ARTAs were enzalutamide in the former and abiraterone in the latter cohort. Median OS was 30.4 and 14.3 months in the sipuleucel-T + ARTA and ARTA monotherapy cohorts, respectively, with the sipuleucel-T + ARTA cohort having a 28.3% lower risk of death than the ARTA monotherapy cohort (hazard ratio 0.717; 95% CI 0.648, 0.793; p < 0.01).

Conclusions: This real-world study of mCRPC treatment indicates that men receiving sipuleucel-T and ARTAs had a longer median OS than patients receiving treatment with an ARTA alone, suggesting that leveraging mechanisms of action can be beneficial in treating patients with mCRPC.

Keywords: Immunotherapy; Observational; Prostate cancer; Real-world evidence; Sequencing; Treatment.

Fig. 1

Illustration of the analysis cohorts used in this study. The action of sipuleucel-T persists after the infusion is finished (light blue bars). The sipuleucel-T + androgen receptor-targeting agent (ARTA) cohort comprised patients who had one of these treatment patterns (A–D). A Initiation of ARTA therapy within 6 months of initiating sipuleucel-T as first-line therapy; sipuleucel-T treatment may be continuing or completed when patients initiate ARTA therapy. B Initiation of sipuleucel-T therapy within 6 months of initiating ARTA as first-line therapy; ARTA treatment completed for 90 days before initiating sipuleucel-T therapy. C Initiation of sipuleucel-T therapy within 6 months of initiating ARTA therapy; ARTA treatment completed for 30 days before initiation of sipuleucel-T therapy. Treatment with sipuleucel-T followed by reinitiation of ARTA therapy; sipuleucel-T treatment may be continuing or completed when patients initiate ARTA therapy. Most patients reinitiate therapy with the same ARTA (abiraterone or enzalutamide) as the initial ARTA. D Initiation of sipuleucel-T within 6 months of initiating ARTA therapy; ARTA treatment completed for at least 30 days before initiation of sipuleucel-T therapy. E ARTA group comprised patients who initiated ARTA therapy and continued to receive ARTA treatment throughout the study period

Fig. 2

Illustration of the study design. Patients with their first claim for an mCRPC treatment in either of the index years (2014 or 2015) were identified. They could not have received treatment for mCRPC in the previous 12 months (look back) and had to have a known outcome during the observation period of up to 36 months (look forward for either death or survival at 36 months). mCRPC metastatic castration-resistant prostate cancer

Fig. 3

Flowchart shows how eligible patients were identified in the Medicare Fee-for-Service 100% research identifiable dataset with the number of patients at each stage. To be eligible, patients had to have continuous Medicare Part A, B, and D eligibility and could not be enrolled in a health maintenance organization. Patients could have received androgen-deprivation treatment. ^aEligibility requirements were having continuous Part A, B, and D eligibility and no health maintenance organization (HMO) enrollment; ^bPatients could have received androgen deprivation treatment; ^cARTA treatments include abiraterone acetate or enzalutamide. mCRPC metastatic castration-resistant prostate cancer

Fig. 4

Impact of the use of sipuleucel-T (SIP-T) in combination with androgen receptor-targeting agent (ARTA) treatment on overall survival by analysis cohort. Median overall survival outcomes were calculated by analysis group. Patients either received sipuleucel-T in combination with ARTA treatment or ARTA only. Patients in the sipuleucel-T + ARTA combination cohort are indicated by a dashed blue line and those in the ARTA monotherapy cohort are indicated by a solid red line. A Graph of Kaplan–Meier estimates of overall survival. This graph illustrates the univariate analysis of overall survival as well as the numbers of patients at risk by treatment cohort and the estimates of unadjusted median overall survival by treatment cohort. B Graph of direct adjusted survivor functions. This graph illustrates the estimates of survival using a direct adjusted survivor function based on the Cox multivariable model. The respective estimates of adjusted median overall survival are also presented. HR hazard ratio

Fig. 5

Forest plot illustrating the impacts of the covariates used in the Cox proportional hazards model. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each of the covariates used in the final model are presented here. See Table 1 for additional information on covariates. ARTA androgen receptor-targeting agent, CCI Charlson Comorbidity Index, continuous continuous variable, mono monotherapy, PDC proportion of days covered, SIP-T sipuleucel-T, SREs skeletal-related events