Real-world outcomes reported for sipuleucel-T

Published findings from PROCEED, a large registry collecting data from men treated with sipuleucel-T (Provenge) for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), provide valuable insight on real-world outcomes associated with this immunotherapy agent in the modern era of prostate cancer management.

The report, published in Cancer (Sept. 4, 2019 [Epub ahead of print]), included data from 1,976 patients who were entered into the registry between 2011 and 2014, of whom 1,902 received one or more sipuleucel-T infusions. The analysis, which was based on a median follow-up of 46.6 months, showed that a substantial proportion of men had a long interval between sipuleucel-T and subsequent therapy; 32.5% of patients experienced a 1-year treatment-free interval and 17.4% of men had a 2-year treatment-free interval, said lead author Celestia S. Higano, MD, professor of medical oncology, department of medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle.

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Median overall survival (OS) after receipt of the immunotherapy was 30.7 months; median time from first sipuleucel-T infusion to prostate cancer-related death was 42.7 months.

A post hoc analysis identified a benefit from earlier initiation of immunotherapy. Median PSA at enrollment for the entire cohort was 15.0 ng/mL, and stratification of men into quartiles by baseline PSA level showed median OS decreased with increasing PSA. Within the lowest PSA quartile (≤5.27 ng/mL), median OS was 47.7 months, and 44% of men did not receive any additional cancer treatments for at least 1 year. Nearly all of the latter men were treated with sipuleucel-T as first-line therapy as recommended by the National Comprehensive Cancer Network, said Dr. Higano.

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“The findings from PROCEED are useful for clinicians in discussing treatment options with patients, particularly those with a low PSA. Considering the prognosis for a man with mCRPC, the median survival of nearly 4 years in men treated with sipuleucel-T when their PSA was low is compelling in suggesting a positive outcome when immunotherapy is given earlier when baseline PSA is lower,” Dr. Higano told Urology Times.

“It is also important to note that the mCRPC treatment space evolved rapidly after the phase III IMPACT trial investigating sipuleucel-T was conducted. Findings from data collected in PROCEED shed new light on the safety and survival outcomes that can be expected when these new therapies are used before and following treatment with sipuleucel-T,” she said.

A total of 338 men (17.8%) received an OS-prolonging anticancer intervention (abiraterone [ZYTIGA], enzalutamide [XTANDI], docetaxel [Taxotere], cabazitaxel [Jevtana], or radium 223 [Xofigo]) before sipuleucel-T, and 1,483 men (78%) received one or more anticancer interventions following receipt of sipuleucel-T.

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Dr. Higano observed that the findings from PROCEED showing better survival outcomes among men treated earlier with immunotherapy when their PSA was lower are consistent with results from the pivotal phase III IMPACT trial. A post hoc analysis of IMPACT data showed men with mCRPC who received sipuleucel-T when their PSA was <22.1 ng/mL had a median OS of 41.3 months, which represented an improvement of 13 months compared to the median OS for the men in the same PSA grouping in the untreated control group.

The safety outcomes recorded in PROCEED were also consistent with the safety profile of sipuleucel-T in the phase III study. In PROCEED, a serious adverse event related to sipuleucel-T occurred in 3.9% of patients; the most common of these events were chills (0.7%) and cerebrovascular accident (0.5%). Overall, a cerebrovascular event occurred in 2.8% of patients, which translates into a rate of 1.2 per 100 person-years. Analysis of data from the Surveillance, Epidemiology, and End Results-Medicare database show a cerebrovascular event rate of 1.5 per 100 person-years among men with mCRPC.

Dr. Higano has served in an advisory role for Aptevo, Asana, Astellas, Bayer, Blue Earth Diagnostics, Churchill Pharma, Clovis Oncology, Dendreon, Endocyte, Ferring, Medivation, Orion Corp., and Pfizer; she has also participated in sponsored research for Aptevo, Bayer, Aragon Pharma, Astellas, AstraZeneca, Dendreon, Genentech, Hoffman-LaRoche, Medivation, Sanofi, and Pfizer, and her spouse was in a leadership role for CTI Biopharma.