The Addition of Sipuleucel-T to Immunotherapy Prolonged Survival in Men with mCRPC

Rana R. McKay, MD

A significant reduction in the risk of death was observed with the addition of sipuleucel-T (Provenge) to either abiraterone acetate (Zytiga) or enzalutamide (Xtandi) as treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in a real-world analysis, Dendreon Pharmaceuticals announced in a press release.¹

The risk of death was reduced by 41% in any line with sipuleucel-T, and the median overall survival (OS) was prolonged by 14.5 months, according to the findings from this analysis of real-world outcomes in men with mCRPC who were treated with sipuleucel-T and the commonly prescribed oral therapies.

“Based on our analysis, men with mCRPC who received sipuleucel-T had a significant improvement in median overall survival and reduction in the risk of death at three years, regardless of line of use,” said lead author Rana R. McKay, MD, medical oncologist and assistant professor of medicine at Moores Cancer Center, University of California, San Diego, in a statement. “These data contribute to a growing body of evidence demonstrating the real-world effectiveness of sipuleucel-T in the mCRPC patient.”

In this retrospective analysis, men with mCRPC who were chemotherapy-naïve at the start of treatment in 2014 and had continuous Medicare Parts A, B, and eligibility during the 3-year observation period were included in the analysis, which compared frontline sipuleucel-T compared with frontline androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate or enzalutamide, which were approved in 2013 and 2014, respectively, for the treatment of men with metastatic prostate cancer who had minimal or no symptoms.²

A multivariable regression model was used to help control for potentially confounding factors while assessing survival outcomes. Overall, 6044 men were included in the study, with the average age of patients being 75 to 78 years. The disease severity was similar among patients in the analysis.

In the overall population, the median OS was 22.97 in this analysis. Among patients in the any-line cohort, the median OS was 35.2 months with the addition of sipuleucel-T compared with 20.7 months in the ASPI arm, while the median OS in the frontline cohort was 34.9 months versus 21.0 months, respectively. The model outcomes demonstrated that the study drug was associated with significantly prolonged OS compared with ASPIs, with an adjusted hazard ratio of 0.59 (95% CI, 0.527-0.651) in the any-line cohort and 0.56 (95% CI, 0.494-0.627) in the frontline cohort.

Patients in the frontline cohort who received the study drug had a 44% reduction in the risk of death at 3 years compared with those who received an ASPI (adjusted HR, 0.56; 95% CI, 0.494-0.627; P <.0001). Similarly, in the frontline cohort, the risk of death at 3 years was reduced 41% with the addition of sipuleucel-T compared with the oral agents alone (adjusted HR, 0.59; 95% CI, 0.527-0.651; P <.0001).

In the frontline cohort, fewer emergency department visits were observed in the first year in patients receiving sipuleucel-T compared with the control arm, although safety was not a primary focus for this analysis. These visits to the emergency departments provide insights on serious adverse events in claims databases, but clinical details are often limited. Regardless of the cause, the median average number of visits per 100 patients within the first year of treatment was 164.3 in the sipuleucel-T arm, 194.5 in the enzalutamide arm, and 206.4 in the abiraterone acetate, and the average number of visits related to prostate cancer were 11.6, 16.0, and 14.1, respectively.

“This analysis underscores the importance of using complementary mechanisms of action to maximize patient survival outcomes and highlights the critical role immunotherapy plays in the modern era of mCRPC treatment,” stated Bruce A. Brown, MD, chief medical officer at Dendreon.¹ “Sipuleucel-T continues to deliver on its promise of helping men with advanced prostate cancer live longer and should be considered when making treatment decisions in daily clinical practice.”

_References

_{1. Real-world evidence shows adding Provenge (sipuleucel-t) to advanced prostate cancer treatment regimen prolonged median survival by 14.5 months. News Release. Dendreon Pharmaceuticals. October 14, 2020. Accessed October 15, 2020. https://bwnews.pr/379QvZq}

_{2. McKay RR, Hafron JM, Ferro C, et al. A retrospective observational analysis of overall survival with sipuleucel-T in medicare beneficiaries treated for advanced prostate cancer [Published Online October 7, 2020]. Advances in Therapy. doi: 10.1007/s12325-020-01509-5}