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

Plain Language Summary The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) continues to evolve. There are multiple treatments for mCRPC, including sipuleucel-T, the first US Food and Drug Administration (FDA)-approved immunotherapy, and the androgen receptor-targeting agents (ARTAs) abiraterone acetate and enzalutamide. Although sipuleucel-T uses a unique mechanism of action that may be useful in developing a treatment strategy for mCRPC, an optimal treatment algorithm for prostate cancer remains undefined. Therefore, survival was compared in men with mCRPC who received sipuleucel-T and an ARTA in the first 6 months of treatment with those who received only ARTA monotherapy. A retrospective longitudinal study was conducted using the US Medicare Fee-for-Service 100% research identifiable dataset linked to the National Death Index. Eligible men started their first mCRPC treatment with either sipuleucel-T or ARTA in either 2014 or 2015 and had continuous Medicare eligibility for the subsequent 3 years. Men who received treatment with both sipuleucel-T and an ARTA had a longer median survival (30.4 months) than men who received an ARTA without sipuleucel-T (14.3 months). This represents a 28% reduced risk of death with sipuleucel-T. This real-world study of mCRPC treatment indicates that men receiving sipuleucel T and an ARTA survive longer than men who only receive an ARTA, suggesting that changing the mechanism of action can be beneficial in treating patients with mCRPC. 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-naive 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.