Overall survival (OS) of African-American (AA) and Caucasian (CAU) men who received sipuleucel-T for metastatic castration-resistant prostate cancer (mCRPC): Final PROCEED analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5035-5035 ◽  
Author(s):  
A. Oliver Sartor ◽  
Andrew J. Armstrong ◽  
Chiledum Ahaghotu ◽  
David G. McLeod ◽  
Matthew R. Cooperberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Sensitivity Analyses ◽  
Number Needed To Treat ◽  
Cancer Therapies ◽  
Matched Cohort ◽  
Castration Resistant Prostate Cancer ◽  
Multivariable Analyses ◽  
Baseline Psa

5035 Background: Prostate cancer risk and mortality are higher in AAs versus CAUs. Post-hoc analyses of pooled Phase 3 data (n = 737) suggested substantial OS benefit for AA men receiving sipuleucel-T (n = 33) vs placebo (n = 10) (McLeod 2012). Compared with pooled placebo patients (n = 249), number needed to treat for OS benefit at 3 years was 3 for AAs and 8 for all sipuleucel-T-treated patients (n = 488) (Moses 2019). Herein we analyzed PROCEED (NCT01306890), a large real-world registry, in which all patients received sipuleucel-T. Methods: In PROCEED, 1902 mCRPC patients received ≥1 sipuleucel-T infusion. OS of all AA (n = 221) and CAU (n = 1649) men were compared. Baseline prostate-specific antigen (PSA), the most important prognostic variable for OS after sipuleucel-T (Schellhammer 2013), substantially differed by race. Thus, OS for a PSA-matched cohort (n = 219 AA; n = 438 CAU) was compared and univariable/multivariable analyses were performed. Post-sipuleucel-T use of OS-prolonging anticancer interventions was also assessed. Results: After a median follow-up of 46.6 mo, median OS was 35.2 (all sipuleucel-T-treated AAs) and 29.9 mo (all sipuleucel-T-treated CAUs): HR 0.81, 95% CI 0.68–0.97; P = 0.03. In the PSA-matched cohort, median OS was 35.3 and 25.8 mo, respectively (HR 0.70, 95% CI 0.57–0.86; P < 0.001). Sipuleucel-T-treated AAs with lower baseline PSA had markedly longer median OS vs sipuleucel-T-treated CAUs. Among those with ≤ median baseline PSA (29.48 ng/ml), median OS was 54.3 mo (AA) vs. 33.4 (CAUs); HR 0.52, 95% CI 0.37–0.72; p < 0.001. Along with other known prognostic factors, AA race was independently associated with prolonged OS on detailed multivariable analyses (HR 0.60, 95% CI 0.48–0.74; p < 0.001) and confirmed on sensitivity analyses. Post-sipuleucel-T life-prolonging anti-cancer therapies were balanced between groups. Conclusions: Sipuleucel-T-treated AAs had significantly improved OS vs sipuleucel-T-treated CAUs. This analysis marks the largest known racial difference in OS in response to any therapy for mCRPC, a finding with implications for both prostate cancer pathophysiology and cancer immunotherapy. Clinical trial information: NCT01306890.

Comparison of enzalutamide and bicalutamide in patients with non-metastatic castration-resistant prostate cancer: Number needed to treat to achieve one additional patient free of clinical progression events.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 228-228
Author(s):  
Lawrence Ivan Karsh ◽  
David F. Penson ◽  
Raoul Concepcion ◽  
Scott Flanders ◽  
Bruce A. Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Absolute Risk ◽  
Specific Antigen ◽  
Additional Patient ◽  
Number Needed To Treat ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Free Psa ◽  
Castration Resistant ◽  
Psa Progression

228 Background: Androgen receptor inhibitors enzalutamide (ENZA) and bicalutamide (BIC) are used to treat metastatic castration-resistant prostate cancer (mCRPC). The Phase 2 STRIVE trial included 35% non-metastatic (m0) and 65% metastatic CRPC patients (pts); ENZA reduced the risk of progression or death among pts, with an adverse event profile consistent with previous trials. The objective of this analysis was to compare ENZA with BIC using the number needed to treat (NNT) to achieve one additional pt with m0CRPC, with either a progression-free survival (PFS) event, radiographic PFS (rPFS), or free of prostate-specific antigen (PSA) progression at 1 year and 2 years. Methods: The 1- and 2-year event rates of PFS, rPFS, and progression-free PSA among pts treated with ENZA and BIC were obtained from the STRIVE trial report. The NNT was calculated as the reciprocal of the absolute risk reduction between ENZA and BIC at each time point. This represents the number of pts that need to be treated with ENZA, compared with BIC, to obtain one additional pt free of a clinical progression event. PFS was defined as the time from randomization to investigator-assessed radiographic (bone or soft tissue) progression, PSA progression, or death. The 95% confidence interval (CI) of the NNT was derived based on the 95% CI of the event rate difference. Results: The NNT to achieve one additional pt with PFS at 1 year, comparing ENZA with BIC, was 2.2 (95% CI 1.7, 3.4), suggesting that treating three pts with ENZA instead of BIC would result in one additional pt free of progression or death at the end of 1 year. The NNT to achieve one additional pt with PFS at 2 years was also 2.2 (95% CI 1.5, 3.7). For rPFS, the NNTs comparing ENZA with BIC were 4.7 (95% CI 2.8, 14.6) and 3.0 (95% CI 2.0, 6.1) at 1 and 2 years, respectively. For progression-free PSA, the NNTs were 2.0 (95% CI 1.5, 2.8) and 2.0 (95% CI 1.4, 3.3) at 1 and 2 years, respectively. Conclusions: This analysis supports the superior clinical benefit of ENZA versus BIC in men with m0CRPC. Pts treated with ENZA showed low NNT values across all clinical outcomes and time points. Clinical trial information: NCT01664923.

scholarly journals Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors

2021 ◽  
Author(s):  
Fred Saad ◽  
Martin Bögemann ◽  
Kazuhiro Suzuki ◽  
Neal Shore
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Conventional Imaging ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Consensus Statements

Abstract Background Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required. Methods In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function. Results and conclusions While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.

Cumulative Prostate Cancer Risk Assessment with the Aid of the Free-to-Total Prostate Specific Antigen Ratio

2004 ◽  
Vol 45 (2) ◽  
pp. 160-165 ◽  
Author(s):  
Gunnar Aus ◽  
Charlotte Becker ◽  
Stefan Franzén ◽  
Hans Lilja ◽  
Pär Lodding ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Assessment ◽  
Cancer Risk ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Cancer Risk Assessment ◽  
Total Prostate Specific Antigen

Bone modifying agents in veterans with castration-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6582-6582
Author(s):  
Jordan Bauman ◽  
Kyle Kumbier ◽  
Jennifer A. Burns ◽  
Jordan Sparks ◽  
Phoebe A. Tsao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Veterans Health ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
National Guidelines ◽  
Castration Resistant ◽  
Unit Increase

6582 Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.

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