Sipuleucel-T Plus Androgen-Receptor Signaling Pathway Inhibitors Boosts OS in Real-World mCRPC Analysis

Rana R. McKay, MD

The addition of sipuleucel-T (Provenge) to the androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate (Zytiga) or enzalutamide (Xtandi) reduced the risk of death by 41% and extended median overall survival (OS) by 14.5 months in patients with metastatic castration-resistant prostate cancer (mCRPC), irrespective of treatment order, according to real-world results from a retrospective observational analysis published in Advances in Therapy.¹

Results showed that in Medicare beneficiaries who received approved treatments for mCRPC, the median OS was significantly prolonged in patients who received treatment with sipuleucel-T versus ASPIs. Specifically, the median OS was 35.2 months with sipuleucel-T versus 20.7 months with ASPIs in the any-line cohort; in the first-line cohort, the median OS was 34.9 months versus 21.0 months, respectively.

Additionally, patients who were given sipuleucel-T in the frontline setting experienced a 44% reduction in the risk of death at 3 years versus those who received oral agents (adjusted HR, 0.56; 95% CI, 0.494-0.627). In the any-line cohort, patients who received sipuleucel-T had a 41% decrease in the risk of death at 3 years compared with those who were given an oral agent alone (adjusted HR, 0.59; 95% CI, 0.527-0.651).

“Based on our analysis, men with mCRPC who received sipuleucel-T had a significant improvement in median OS and reduction in the risk of death at 3 years, regardless of line of use,” said Rana R. McKay, MD, lead author of the study, as well as medical oncologist and assistant professor of medicine at Moores Cancer Center of the University of California, San Diego.² “These data contribute to a growing body of evidence demonstrating the real-world effectiveness of sipuleucel-T in [patients with] mCRPC.”

Sipuleucel-T is an autologous antigen-presenting cell vaccine that is developed by co-culturing leukapheresed immune cells with a fusion protein comprised of prostatic acid phosphatase and granulocyte macrophage colony–stimulating factor. When infused, the activated antigen-presenting cells within the agent rouse effector T cells which produces an antitumor effect.

In April 2010, sipuleucel-T received FDA approval for use in patients with asymptomatic or minimally symptomatic mCRPC. However, since this regulatory decision, the ASPIs abiraterone acetate and enzalutamide were also approved for use in the same population. The ASPIs have become the most frequently utilized agents in mCRPC and the National Comprehensive Cancer Network guidelines recommend both sipuleucel-T and ASPIs for use in the frontline setting.

In the study, investigators set out to compare the effectiveness of sipuleucel-T and ASPIs in improving OS in men treated for advanced prostate cancer per the Medicare 100% dataset. They examined the subset of patients with advanced disease who had not received chemotherapy at the start of each type of treatment. Investigators used multivariate modeling to control for those factors that were measurable in the dataset. By examining the Medicare dataset, they were able to access longitudinal data necessary for the analysis.

The retrospective cohort analysis included data from Medicare claims for 6044 fee-for-service beneficiaries who received treatment between 2013 and 2017. The average age of those included in the analysis ranged from 75 to 78 years and over 80% were white. The analysis was comprised of 2 comparisons. The first compared patients who received sipuleucel-T during some line of treatment, and any other approved agent, compared with patients treated with 1 of the ASPIs during any line of treatment, and any other agent except sipuleucel-T.

The other comparison was patients who received sipuleucel-T in the frontline compared with those who received abiraterone acetate or enzalutamide in the frontline setting. In subsequent lines, patients in either of those groups could receive any other drug approved for mCRPC. Patients in the frontline ASPI were able to receive sipuleucel-T in the second-line setting or later.

In the first-line setting, sipuleucel T was used in 10.8% of patients, enzalutamide in 24.3%, abiraterone in 55.9%, docetaxel in 8.7%, and cabazitaxel in 0.3%. In the second-line setting, sipuleucel-T was used in 4.8% of patients, enzalutamide in 48%, abiraterone in 24.5%, docetaxel in 15.5%, cabazitaxel in 1.2%, and radium-223 (Xofigo) in 6%. In the third-, fourth-, and fifth-line settings, sipuleucel-T was used by 3.8%, 5.2%, and 0% of patients, respectively.

With regard to safety, the use of sipuleucel-T in the frontline setting led to fewer emergency department visits in the first year versus the oral agents.

“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,” said Bruce A. Brown, MD, chief medical officer at Dendreon.² “[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. 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. Adv Ther. Published online October 7, 2020. https://bit.ly/33Z9ioj.
2. 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 14, 2020. https://bwnews.pr/2SSbKGI.