Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry

Abstract

Purpose African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. Patients and methods OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan-Meier and Cox proportional hazard methodologies. Results Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68-0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57-0.86, P < 0.001) in the PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37-0.72, P < 0.001), with median OS of 54.3 versus 33.4 months. Known prognostic factors and African American race (multivariable analyses; HR: 0.60, 95% CI: 0.48-0.74, P < 0.001) were independently associated with OS. Use of post-sipuleucel-T anticancer interventions was balanced between races. Conclusion In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

A Retrospective Observational Analysis of Overall Survival with Sipuleucel-T in Medicare Beneficiaries Treated for Advanced Prostate Cancer

“…The ‘risk’ variables included in our overall survival multivariable analysis (e.g., presence of multiple metastases, presence of SREs, Charlson Comorbidity Index score, chronic opiate use, and corticosteroid use) were all found to associate with decreased survival (Table 2 )–providing internal validation that these covariates were prognostic factors of disease. Race was also a significant covariate, with black race being associated with improved outcomes, a finding consistent with previous studies [ 31 – 33 ]. Several key variables (e.g., cancer-related pain) are not available and have to be inferred on the basis of claims-level data (e.g., opiate usage).…”

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration

“…These collectively demonstrate that DNA repair pathway genes, mutations in SPOP , and DNA repair signatures are increased in African American men, which may suggest enhanced responses to radiation therapy, although further studies are warranted to test this hypothesis 21‐23 . Differential responses to systemic therapy between Black and White patients with castration‐resistant prostate cancer have been observed with sipuleucel‐T, 24 radium‐223, 25 and androgen receptor‐targeting agents 26 . Furthermore, data from The Cancer Genome Atlas of men of predominant African ancestry versus European ancestry demonstrated substantial heterogeneity in the prostate tumor genome and transcriptome, suggesting biologic contributors to racial disparities 27 …”

Genomic Profiling of Prostate Cancers from Men with African and European Ancestry

“…Determining a comprehensive understanding of the genomic features of AFR prostate cancers and how they relate to adverse features or contribute to poorer outcomes overall for AFR men could inform our strategies to improve precision medicine for these patients. These studies will remain important to understand when certain therapies may preferentially benefit AFR patients, who remain underrepresented in clinical trials (30). Examining additional features such as the noncoding genome, epigenome, and tumor microenvironment will be needed to fully understand the biological contribution to the observed disparities in incidence and mortality for AFR men.…”