Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry.

Prostate cancer disproportionately affects racial and ethnic minority populations. Reasons for disparate outcomes among minority patients are multifaceted and complex, involving factors at the patient, provider, and system levels. Although advancements in our understanding of disease biology have led to novel therapeutics for men with advanced prostate cancer, including the introduction of biomarker-driven therapeutics, pivotal translational studies and clinical trials are underrepresented by minority populations. Despite attempts to bridge the disparities gap, there remains an unmet need to expand minority engagement and participation in clinical trials to better define the impact of therapy on efficacy outcomes, quality of life, and role of biomarkers in diverse patient populations. The IRONMAN registry (ClinicalTrials.gov identifier: NCT03151629), a global, prospective, population-based study, was borne from this unmet medical need to address persistent gaps in our knowledge of advanced prostate cancer. Through integrated collection of clinical outcomes, patient-reported outcomes, epidemiologic data, and biospecimens, IRONMAN has the goal of expanding our understanding of how and why prostate cancer outcomes differ by race and ethnicity. To this end, the Diversity Working Group of the IRONMAN registry has developed informed strategies for site selection, recruitment, engagement and retention, and trial design and eligibility criteria to ensure broad inclusion and needs awareness of minority participants. In concert with systematic strategies to tackle the complex levels of disparate care, our ultimate goal is to expand minority engagement in clinical research and bridge the disparities gap in prostate cancer care.

Treatment of metastatic castration resistant prostate cancer with radium-223: a retrospective study at a US tertiary oncology center.

BACKGROUND: Guidelines for optimal sequencing of radium-223 and chemotherapy for metastatic castration resistant prostate cancer (mCRPC) do not exist. This study evaluated treatment patterns and overall survival (OS) among patients with mCRPC treated with radium-223 in an academic clinical setting. METHODS: A retrospective study was conducted of bone metastases-predominant mCRPC patients treated with radium-223. Treatment patterns from 2013 to 2018 were evaluated in patients treated with radium-223 pre- vs. post-chemotherapy. OS was examined using Kaplan-Meier medians and 95% confidence intervals. RESULTS: In total, 220 patients were treated with radium-223 (64 pre-chemotherapy, 83 post-chemotherapy, 73 no chemotherapy). Mean radium-223 injections per patient was 5.3 and 4.3 in the pre- vs. post-chemotherapy cohorts, respectively (p < 0.001). The number of chemotherapy cycles was similar for chemotherapy given pre- or post-radium-223. Mean line of mCRPC therapy of radium-223 was 3rd and 5th when given pre- and post-chemotherapy, respectively (p < 0.001). 41.8% patients were treated with radium-223 in combination with another mCRPC therapy, commonly abiraterone acetate (43.5%) or enzalutamide (52.2%). The majority received combination therapy for the duration of radium-223 treatment; 20.7% started another agent after radium-223 initiation; 20.7% initiated radium-223 while on established therapy. Median OS from first mCRPC treatment was 39.4 months (95% CI 33.0, 48.8) for patients with radium-223 pre-chemotherapy vs. 37.4 months (95% CI 32.0, 43.5) post-chemotherapy (and 35.2 months [95% CI 27.9, 43.3] vs. 32.0 months [95% CI 26.9, 36.0] for patients with radium-223 combination vs. monotherapy). CONCLUSIONS: This retrospective analysis of patients treated with radium-223 demonstrates that administration of radium-223 pre-chemotherapy increased likelihood of completion of radium-223 treatment. Radium-223 given pre- or post-chemotherapy and with or without combination therapy did not result in significant differences in OS. Additional studies are needed to determine the optimal sequencing strategy of mCRPC in the modern era.

Patient and caregiver benefit-risk preferences for nonmetastatic castration-resistant prostate cancer treatment.

BACKGROUND: Recently approved second-generation androgen receptor inhibitors (SGARIs) for non-metastatic castration-resistant prostate cancer (nmCRPC) have similar efficacy but differ in safety profiles. We used a discrete choice experiment (DCE) to examine how nmCRPC patients and caregivers perceive the benefits versus risks of these new treatments. METHODS: An online DCE survey with 14 treatment choice questions was administered to nmCRPC patients and caregivers. Each choice question compared two hypothetical medication profiles varying in terms of 5 safety attributes (risk or severity of adverse events [AEs]: fatigue, skin rash, cognitive problems, serious fall, and serious fracture) and two efficacy attributes (duration of overall survival [OS] and time to pain progression). Random parameters logit models were used to estimate each attribute's relative importance. We also estimated the amounts of OS that respondents were willing to forego for a reduction in AEs. RESULTS: In total, 143 nmCRPC patients and 149 caregivers viewed the AEs in following order of importance (most to least): serious fracture, serious fall, cognitive problems, fatigue, and skin rash. On average, patients were willing to trade 5.8 and 4.0 months of OS to reduce the risk of serious fracture and fall, respectively, from 3% to 0%; caregivers were willing to trade 6.6 and 5.4 months of OS. CONCLUSIONS: nmCRPC patients and caregivers preferred treatments with lower AE burdens and were willing to forego OS to reduce the risk and severity of AEs. Our results highlight the importance of carefully balancing risks and benefits when selecting treatments in this relatively asymptomatic population.

Physician preferences for non-metastatic castration-resistant prostate cancer treatment.

BACKGROUND: Recent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). These SGARIs have similar efficacy but differ in safety profiles. We used a discrete choice experiment to explore how United States physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC, a largely asymptomatic disease. METHODS: Treating physicians (n = 149) participated in an online survey that included 14 treatment choice questions, each comparing 2 hypothetical treatment profiles, which varied in terms of 5 safety and 2 efficacy attributes. We described safety attributes (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency, and efficacy attributes (overall survival [OS] and time to pain progression) in terms of duration of effect. We used a random parameters logit model to estimate preference weights and importance scores for each attribute. We also estimated the amount of survival gain physicians were willing to trade for a reduction in specific AEs between treatment options. RESULTS: Physicians placed more importance on survival than on time to pain progression, and viewed a reduction in cognitive problems from severe to none, a reduction in risk of a serious fracture from 8% to none, and a reduction in fatigue from severe to none as the most important safety attributes. Physicians were willing to forego 9.1 and 6.6 months of OS, respectively, to reduce cognitive problems and fatigue from severe to mild-to-moderate. To reduce the risk of a serious fracture from 8 to 5% and 5% to none, physicians were willing to trade 3.9 and 5.3 months of OS, respectively. CONCLUSIONS: Physicians were willing to trade substantial amounts of survival to avoid AEs between hypothetical treatments. These results emphasize the importance of carefully balancing therapies' benefits and risks to ultimately optimize the overall quality of nmCRPC patients' survival. Nonetheless, it is noted that the results from the study sample of 149 physicans may not be representative of the viewpoints of all nmCRPC-treating physicians.

Diversity of Enrollment in Prostate Cancer Clinical Trials: Current Status and Future Directions.

BACKGROUND: Although there are considerable racial and ethnic disparities in prostate cancer incidence and mortality in the United States and globally, clinical trials often do not reflect disease incidence across racial and ethnic subgroups. This study aims to comprehensively review the reporting of race and ethnicity data and the representation of race and ethnicity across prostate cancer treatment-, prevention-, and screening-based clinical trials. METHODS: Seventy-two global phase III and IV prevention, screening, and treatment prostate cancer clinical trials with enrollment start dates between 1987 and 2016 were analyzed in this study, representing a total of 893,378 individual trial participants. Availability and representation of race and ethnicity data by trial funding type, temporal changes in the racial/ethnic diversity of participants, and geographic representation of countries were assessed. RESULTS: Of the 72 trials analyzed, 59 (81.9%) had available race data, and 11 (15.3%) of these trials additionally reported ethnicity. Of the trials reporting data, participants were overwhelmingly white men (with the highest proportion in U.S. nonpublicly funded trials), comprising over 96% of the study population. The proportion of white participants in prostate cancer clinical trials has remained at over 80% since 1990. Geographically, Africa and the Caribbean were particularly underrepresented with only 3% of countries included. CONCLUSIONS: Trial participants continue to be majority white despite the known racial disparities in prostate cancer clinical outcomes. IMPACT: Current and future trials must use novel recruitment strategies to ensure enrollment of underrepresented men. Targeting the inclusion of African and Caribbean medical centers is crucial to achieve equity in representation.

A Retrospective Claims Analysis of Advanced Prostate Cancer Costs and Resource Use.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is associated with high costs and healthcare resource utilization (HCRU). OBJECTIVE: This study followed patients with CRPC through their continuum of care and analyzed claims data regarding treatments, total HCRU, and costs, both before and after metastasis diagnosis. METHODS: A retrospective cohort of patients with newly diagnosed metastatic CRPC (mCRPC) in the USA was identified from the Truven Health MarketScan database from January 2009 to March 2015. The mCRPC algorithm employed International Classification of Diseases, Ninth Revision codes for prostate cancer (pre-index) and secondary metastatic disease (index date) and a subsequent claim for a US FDA-approved treatment for mCRPC. Patient inclusion required evidence of surgical or pharmacological castration and no evidence of bone-targeted treatments during the baseline period while evaluating continuous enrollment 25 months pre-index and 6 months post-index. Treatment patterns were assessed during pre- and post-index periods; HCRU and costs were annualized for comparison purposes regarding both pre- and post-index timeframes. RESULTS: Among 261 patients with mCRPC (mean age 72 years), the most common treatments during the pre-index period were bicalutamide (90.04%), leuprolide (81.99%), abiraterone (22.22%), docetaxel (20.69%), and ketoconazole (18.01%). Mean per-patient-per-year (PPPY) all-cause annualized healthcare costs significantly increased from $US35,102.55 in the pre-index nonmetastatic CRPC (nmCRPC) period to $US156,499.89 after metastasis diagnosis (mCRPC). Mean PPPY inpatient admissions and emergency department visits increased from 0.20 to 1.36 and from 0.63 to 1.56, respectively. CONCLUSIONS: Average yearly costs and HCRU were four times higher following mCRPC diagnosis, indicating a need for appropriate management strategies to optimize the potential delay of disease progression among patients with nmCRPC.

Real-World Treatment Patterns in Patients with Castrate-Resistant Prostate Cancer and Bone Metastases.

BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in men in the United States. There is scant real-world evidence characterizing the care utilization and clinical outcomes associated with the use of therapies currently approved by the US Food and Drug Administration (FDA) for patients with metastatic castrate-resistant prostate cancer (CRPC). OBJECTIVE: To describe the real-world treatment patterns, healthcare costs, and survival rates of patients with metastatic CRPC and bone metastases who have commercial or Medicare coverage. METHODS: This retrospective observational study was conducted using medical and pharmacy claims from the Humana research database for male patients who had Medicare or commercial coverage and were aged 55 to 89 years at the initiation of treatment for metastatic CRPC. Three inclusion criteria were used to identify appropriate patients for the 2 cohorts, including (1) a diagnosis of prostate cancer (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 185.x); (2) a diagnosis of bone metastasis (ICD-9-CM code 198.5) between 2013 and 2014; and (3) a healthcare insurance claim indicating a prescription for an FDA-approved first-line treatment for metastatic CRPC. Subsequent lines of treatment were also identified through the healthcare claims data. The 2-year survival rate was calculated and controlled for demographic and clinical characteristics, and the total costs (medical plus pharmacy) were calculated for the 6 months postindex. RESULTS: A total of 1855 patients met the study inclusion criteria. Of these patients, 660 (35.6%) received at least 1 medication. The patient count by line of treatment was 660 (100%) who received first-line therapy, 380 (57.6%) who received second-line treatment, 204 (30.9%) who received third-line therapy, and 107 (16.2%) who received fourth-line therapy. The medication distribution by line of treatment (using first-, second-, third-, or fourth-line therapy for each drug) was abiraterone acetate (50.5%, 61.3%, 68.6%, 75.7%); enzalutamide (15.6%, 39.2%, 54.4%, 71.0%); sipuleucel-T (9.2%, 13.9%, 20.1%, 20.6%); radium-223 dichloride (1.7%, 2.6%, 7.4%, 13.1%); cabazitaxel (2.3%, 5.5%, 16.2%, 19.6%); and docetaxel (22.1%, 32.1%, 42.6%, 48.6%). The total monthly unadjusted healthcare costs for patients who received an FDA-approved treatment was much higher ($9435) than for patients with metastatic prostate cancer who did not receive an FDA-approved treatment ($5055), and the 2-year survival rate for patients who received an FDA-approved treatment was 57.1% (25th percentile, 250 days; 50th percentile, 541 days). CONCLUSIONS: The most common first-line treatment for patients with commercial or Medicare coverage who had metastatic CRPC was abiraterone or enzalutamide. Hormone therapies used as monotherapy were the most frequently used treatment, and their concomitant administration with other treatments was the second most common treatment pattern. Additional clinical studies are needed to further elucidate the treatment sequencing for patients with metastatic CRPC.

Costs and Healthcare Resource Utilization Associated with Hospital Admissions of Patients with Metastatic or Nonmetastatic Prostate Cancer.

BACKGROUND: Limited published information exists that compares the costs of metastatic prostate cancer with nonmetastatic prostate cancer. Although most research has focused on the costs of metastatic prostate cancer, delaying metastases in patients with nonmetastatic prostate cancer can reduce or delay healthcare resource utilization and any associated expenditures. OBJECTIVE: To compare the costs and healthcare resource utilization of patients with metastatic or nonmetastatic prostate cancer who were receiving care in an inpatient or an outpatient hospital setting. METHODS: Claims from between June 2010 and September 2016 of patients with metastatic or nonmetastatic prostate cancer were retrospectively identified from the Premier Healthcare Database. Patients with a primary diagnosis of malignant neoplasm of the prostate in the inpatient or outpatient setting during the study period were included. Admissions were categorized as metastatic or nonmetastatic prostate cancer based on the presence or absence of an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and/or ICD-10-CM code for metastatic prostate cancer on discharge. Patients with a secondary diagnosis of distant skeletal, lymph node, or visceral metastasis or who received ≥1 treatments indicative of bone metastasis on the same admission were considered to have metastatic prostate cancer. RESULTS: The study included prostate cancer admissions totaling 78,667 inpatient (4576 with metastatic disease) and 874,366 outpatient (71,545 with metastatic disease) admissions. Among the metastatic prostate cancer inpatient admissions, 72.6% of the patients were aged ≥65 years (mean age, 72 years for metastatic disease vs 63 years for nonmetastatic disease) and approximately 77.5% of these patients had bone metastases. The mean total cost per inpatient admission was $12,324 (standard deviation [SD], $13,506) for metastatic prostate cancer versus $10,987 (SD, $6912) for nonmetastatic disease. The mean total cost per outpatient admission was $1627 (SD, $6182) for metastatic versus $909 (SD, $3458) for nonmetastatic prostate cancer. CONCLUSIONS: The results of this study demonstrate the increased economic burden associated with hospital admissions, particularly inpatient admissions, for patients with metastases compared with patients without metastases. In addition to the clinical burden on patients, these findings further highlight the importance of implementing treatment strategies that can delay progression to metastatic prostate cancer and subsequent increases in healthcare resource utilization and cost.

A qualitative evaluation of the validity of published health utilities and generic health utility measures for capturing health-related quality of life (HRQL) impact of differentiated thyroid cancer (DTC) at different treatment phases.

PURPOSE: This study explored the impact of differentiated thyroid cancer (DTC) on health-related quality of life (HRQL) at different treatment phases and evaluated the validity of published DTC utilities and generic health utility measures (EQ-5D and SF-6D) for economic evaluation of treatments for radio-iodine (RAI) refractory DTC. METHODS: Focus groups and interviews were conducted with DTC patients grouped by treatment phase. Qualitative thematic analysis was conducted on interview/focus group transcripts. A thematic coding framework was developed to compare experiences between treatment phases and inform development of a conceptual model. Model concepts were mapped to EQ-5D and SF-6D domains/items. RESULTS: Eight focus groups and 11 individual interviews were conducted with 52 DTC patients. Fifty symptoms and HRQL concepts were identified. The impact of DTC and DTC treatment on emotional and cognitive functioning was reported across the treatment phases. The impact on daily activities, mobility, and energy levels was greatest for patients with recurring/persistent or RAI-refractory DTC. Of the 50 concepts, 25 and 27 mapped directly onto domains/items in the EQ-5D and SF-6D, respectively. The SF-6D covered a broader range of DTC impact on emotional/physical problems and daily/social activities than did the EQ-5D. CONCLUSIONS: The conceptual model summarizes the wide-ranging impact of DTC and its treatment on patients' HRQL, particularly for those with recurring/persistent or RAI-refractory DTC. Findings suggest that published DTC utilities lack validity for RAI-refractory DTC and that the SF-6D may be more sensitive to HRQL impact of DTC than the EQ-5D.