Conflict of Interest
Request Clinical TrialsAssociated Trial(s):
- NCT00638690 - A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy
- NCT00887198 - A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer
- NCT01695135 - A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (JNJ-212082) Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy
- NCT01867710 - A Randomized Phase 2 Study Evaluating Abiraterone Acetate With Different Steroid Regimens for Preventing Symptoms Associated With Mineralocorticoid Excess in Asymptomatic, Chemotherapy-naïve and Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients
- NCT01715285 - A Randomized, Double-blind, Comparative Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Subjects With High-Risk, Metastatic Hormone-naive Prostate Cancer (mHNPC)
- NCT01591122 - A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (JNJ-212082) Plus Prednisone in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer
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Data Request StatusStatus: Withdrawn/Closed
Project Title: The Impact of Second Generation Anti-Androgens on Quality of Life in Men with Advanced Prostate Cancer
Background: Prostate cancer is the most common malignancy in men, and the second most common cause of male cancer-related death (1). In the last decade, a new generation of anti-androgen drugs have been shown to improve overall survival in men with advanced prostate cancer, particularly those with castrate-resistant disease (2). This class of drugs includes abiraterone, apalutamide, darolutamide, and enzalutamide. Several large clinical trials have been conducted to assess the efficacy and serious adverse events of each of these medications, but the secondary quality-of-life outcomes of these studies have not been fully explored.
Objective: We aim to use survey data from existing clinical trials to determine the impact of second-generation anti-androgens on quality of life in men with advanced prostate cancer.
Study Design: We have identified 9 clinical trials on anti-androgens with data repositories available for public access. Each of these trials had patients answer questions on quality of life using the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire before and after the initiation of treatment. We will compare changes in FACT-P scores by type of anti-androgen as well as by anti-androgen vs. placebo. We hypothesize that second generation anti-androgens will have no impact on quality of life scores compared to placebo.
Participants: Participants in this study include men with advanced prostate cancer who have already participated in existing clinical trials for abiraterone, apalutamide, darolutamide, or enzalutamide and have completed a FACT-P questionnaire both before and after treatment.
Main Outcome Measure: The main outcome measure is change in FACT-P questionnaire score from baseline assessment to 6 month assessment.
Statistical Analysis: R Statistical software will be used for all assessments. Analysis of variance will be used to compare the average change in FACT-P score between different anti-androgen medications and and between anti-androgen medications and placebo . Curves will be created to visually depict the change in quality of life score over time for anti-androgens and placebo. A multivariate regression will be created to identify independent predictors of quality of life preservation.
Brief Project Background and Statement of Project Significance:
Prostate cancer is the most common cancer diagnosed in men and the second most common cause of male cancer-related death (1). As PSA screening has declined in the United States, the incidence of locally advanced and metastatic prostate cancer has increased (3 - 4). In the last decade, a second generation of anti-androgen drugs have been shown to improve overall survival in men with advanced prostate cancer, particularly those with castrate-resistant disease (2). This class of drugs includes abiraterone, apalutamide, darolutamide, and enzalutamide.
There is currently a dearth of existing research regarding how these medications affect quality of life. We aim to use an aggregate of existing data from clinical trials that demonstrated the efficacy of these medications to answer these questions. Men in these trials completed quality-of-life surveys before, during, and after treatment. We aim to use this data to perform a meta-analysis on the quality-of-life changes from second generation anti-androgens.
Specific Aims of the Project:
Aim #1: To measure how second-generation anti-androgen impacts quality-of-life based on responses to the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire in men with advanced prostate cancer compared to each other and compared to placebo. We hypothesize that men initiated on second generation anti-androgens will experience no significant quality of life changes.
Aim #2: To identify independent predictors of quality of life preservation in men with advanced prostate cancer. We predict that response to second generation anti-androgen treatment will be an independent predictor of preserved quality-of-life.
What is the purpose of the analysis being proposed? Please select all that apply.: New research question to examine treatment effectiveness on secondary endpoints and/or within subgroup populations
Software Used: R
Data Source and Inclusion/Exclusion Criteria to be used to define the patient sample for your study:
We have identified 10 clinical trials that tested a second generation anti-androgen in men with prostate cancer and are available by request in public repositories. Each of these trials had patients complete the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire before and after treatment. We will include all patients who participated in these trials and completed the erectile function and sexual satisfaction questions in the FACT-P questionnaire before and after initiation of treatment. Patients who did not complete the sexual function questions before and after treatment will be excluded.
We will obtain data from additional trials outside of YODA. From Clinical Study Data Request, we will obtain NCT01302041, which is a randomized controlled trial evaluating enzalutamide, and NCT02200614, which is a randomized controlled trial evaluating darolutamide. From Vivli, we will obtain NCT01212991 and NCT01664923, which are randomized controlled trials evaluating enzalutamide. As part of our analysis, participant-level data from these outside studies will be combined with data from YODA trials to perform a meta-analysis.
Primary and Secondary Outcome Measure(s) and how they will be categorized/defined for your study: The main outcome measure is change in FACT-P questionnaire score from baseline to 6 month assessment. This score is based on 39 items that are answered via a five point Likert scale ranging from 0 to 4. The change in overall score will be calculated by subtracting the score at baseline assessment from the score at 6 month assessment, which is defined as any assessment within 5 to 7 months after treatment initiation. This value can range from -156 to +156. Changes in scores will also be measured at 1 month, 3 month, and 12 month time periods, as well as the change from initial to final assessment collected.
Main Predictor/Independent Variable and how it will be categorized/defined for your study: The independent variable will be anti-androgen drug administered, with the options being abiraterone, apalutamide, darolutamide, enzalutamide, and placebo. We will categorize this variable as the clinical trial study arm into which each patient was enrolled, staying consistent with the intention-to-treat analysis that was used in the initial study designs.
Other Variables of Interest that will be used in your analysis and how they will be categorized/defined for your study: Other variables that we will examine include age, Eastern Cooperative Oncology Group (ECOG) performance status, duration of time spent on study drug, which will be defined as the time in months on which patients received the study drug prior to final FACT-P assessment, prior cancer treatment received, which will include any treatment of prostate cancer that a patient has received prior to study enrollment, including radical prostatectomy, pelvic radiation, and androgen deprivation therapy. We will also analyze extent of disease, which will be defined as non-metastatic hormone-naive prostate cancer, metastatic hormone-naive prostate cancer, non-metastatic castrate-resistant prostate cancer, or metastatic castrate-resistant prostate cancer.
Statistical Analysis Plan: All patients who completed a baseline FACT-P questionnaire and at least one post-treatment questionnaire will be included in analysis. Baseline characteristics between independent variable groups will be compared using analysis of variance (ANOVA) for continuous variables and and Pearson's chi-squared test for categorical variables. Curves will be created of change in FACT-P scores over time for each independent variable category. Linear regression will be used to identify any strong trends in these curves. ANOVA will be used to compare change in FACT-P score between independent variable groups. A multivariable regression will be created to identify independent predictors of quality-of-life preservation, which will be defined as patients whose FACT-P Scores either improves, remains the same, or decreases by fewer than 8 points. We do not anticipate significant records with missing information given the strict inclusion criteria from these randomized controlled trials. However, for the purpose of multivariate regression, patients with missing values will be excluded from analysis. All analysis will be conducted using R statistical software.
Narrative Summary: Second generation anti-androgens have recently gained FDA approval for their ability to improve survival in men with advanced prostate cancer. However, the impact these medications have on erectile and sexual function has not been investigated. We aim to use an aggregate of existing data from clinical trials that demonstrated the efficacy of these medications to answer these questions. Men in these trials completed quality of life surveys before, during, and after treatment. We aim to use this data to characterize the effect of second generation anti-androgens have on quality of life.
Project Timeline: We anticipate having all clinical trial data in hand by February 1, 2021. Data analysis should be completed by April 1, 2021. A manuscript will be drafted by May 1, 2022 and submitted for publication by June 1, 2022. We plan to report results back to the YODA Project after manuscript acceptance for publication, which we anticipate will occur by August 1, 2022.
Dissemination Plan: Based on this research, we intend to create a manuscript with the results of our data. The manuscript will be intended for urologists and genitourinary oncologists who treat patients with prostate cancer. Potentially suitable journals for this manuscript include the Journal of Urology, European Urology, and Urologic Oncology.
1. Sweeney CJ, Chen YH, Carducci M et al: Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; 373:737.
2. Rice MA, Malhotra SV, Stoyanova T. Second-Generation Antiandrogens: From Discovery to Standard of Care in Castration Resistant Prostate Cancer. Front Oncol. 2019;9:801. Published 2019 Aug 28. doi:10.3389/fonc.2019.00801
3. Shoag J, Halpern JA, Lee DJ, Mittal S, Ballman KV, Barbieri CE, Hu JC. Decline in Prostate Cancer Screening by Primary Care Physicians: An Analysis of Trends in the Use of Digital Rectal Examination and Prostate Specific Antigen Testing. J Urol. 2016 Oct;196(4):1047-52. doi: 10.1016/j.juro.2016.03.171. Epub 2016 Apr 6. PMID: 27060052.
4. Siegel DA, O?Neil ME, Richards TB, Dowling NF, Weir HK. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity ? United States, 2001?2017. MMWR Morb Mortal Wkly Rep 2020;69:1473-1480. DOI: http://dx.doi.org/10.15585/mmwr.mm6941a1external icon