Real-world utilization and outcomes of docetaxel among older men with metastatic prostate cancer: a retrospective population-based cohort study in Canada.

BACKGROUND: The adoption of docetaxel for systemic treatment of metastatic prostate cancer (PCa), in both castration-sensitive (mCSPC) and castration-resistant (mCRPC) settings, is poorly understood. This study examined the real-world utilization of docetaxel in these patients and their outcomes. METHODS: A retrospective population-based study used administrative data from Ontario, Canada, to identify men aged ≥66 years who were diagnosed with de novo mCSPC or mCRPC between 2014 and 2019 and received docetaxel. The study assessed treatment tolerability and toxicity, and survival in both cohorts. Descriptive and comparative statistical analysis were conducted. RESULTS: The study identified 11.2% (399/3556) and 13.2% (203/1534) patients diagnosed with de novo mCSPC and with mCRPC who received docetaxel respectively. The median age in both cohorts was 72 years (IQR: 68-76). Overall, 43.9% (n = 175) patients with de novo mCSPC and 52.1% (n = 85) with mCRPC completed ≥6 cycles of docetaxel. Over two-fifth also needed dose adjustments in both cohorts. Hospitalization or emergency department visit for febrile neutropenia were noted in 15.8% (n = 63) of de novo mCSPC patients and similarly in 19% (n = 31) of mCRPC cohort. The median survival of PCa patients who completed ≥6 cycles of docetaxel was significantly longer relative to those who completed <4 cycles: 32.7 vs. 23.5 months (p < 0.001) for mCSPC and 20.5 vs. 10.7 (p = 0.012) for mCRPC respectively. CONCLUSIONS: In this population-based study of elderly patients with metastatic PCa, treatment with docetaxel was associated with poor tolerability and higher toxicity compared with clinical trials. Receipt of limited cycles and reduced overall dose of docetaxel were associated with inferior overall survival.

Laying the foundation for Real-world evidence studies: a case study from Newfoundland and Labrador.

The Janssen and Newfoundland and Labrador Health Innovation Partnership (JANL-HIP) was established to carry out Real-World Evidence (RWE) projects to generate evidence about disease pathways, healthcare delivery, the effects of clinical interventions. Doing so will support and influence clinical decision-making in Newfoundland and Labrador (NL). This case study describes the foundational elements necessary for a real-world evidence generation project in NL and may provide learning for the effective execution of real-world studies in other jurisdictions. It uses an ongoing project in psoriatic disease in NL to illustrate the partnership and the benefits of RWE studies. Ultimately, the JANL-HIP RWE project aims to inform decisions that will drive improvements in health outcomes, system delivery, and policy mutually beneficial to health ecosystem stakeholders.

Real-World Use of Androgen-Deprivation Therapy: Intensification Among Older Canadian Men With de Novo Metastatic Prostate Cancer.

Background: Despite the wealth of evidence demonstrating the efficacy of treatment intensification beyond androgen-deprivation therapy (ADT) among patients with de novo metastatic castration-sensitive prostate cancer (mCSPC), little is known of its real-world use. This study examined the real-world uptake of ADT treatment intensification among older men in a large Canadian province. Methods: We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. Patients 66 years of age and older with de novo mCSPC were included and their treatment with conventional ADT-based regimens, ADT plus next-generation androgen receptor axis-targeted therapy, and ADT plus docetaxel were identified and stratified by time. Results: From 2014 to 2019, 3556 patients were identified with de novo mCSPC. Most patients (n = 2794 [78.6%]) were treated with a conventional ADT regimen, whereas 399 (11.2%) patients received ADT intensification with docetaxel and 52 (1.5%) patients received abiraterone acetate plus prednisone. In a time-stratified analysis of ADT intensification before and after the pivotal AA+P trial (LATITUDE), AA+P uptake increased from 0.5% to 3.0%, whereas docetaxel use dropped from 12.0% to 10.0%. The median survival of the study population was 18 months (interquartile range = 10-31). Conclusions: The majority of patients with de novo mCSPC are treated with ADT alone in the Canadian real-world setting, despite randomized clinical trial evidence of benefit with the use of ADT-intensified regimens. As ADT treatment intensification is substantially underused, better understanding of the barriers to treatment and targeted education to address them are needed.

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada.

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71-83). The median survival was 18 months (IQR: 10-31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Real-world management of advanced prostate cancer: A description of management practices of community-based physicians and prostate cancer specialists.

INTRODUCTION: The Canadian Genitourinary Research Consortium (GURC) conducted a consensus development conference leading to 31 recommendations. Using the GURC consensus development questionnaire, we conducted a survey to measure the corresponding community-based practices on the management of metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). METHODS: An 87-item online questionnaire was sent to 600 community urologists and oncologists involved in the treatment of prostate cancer. RESULTS: Seventy-two community physicians responded to the survey. Of note, 50% community physicians indicated they would treat nmCRPC with agents approved for this indication if advanced imaging showed metastases. Radiation to the prostate for low-volume mCSPC was identified as a treatment practice by 27% of community physicians, and 35% indicated docetaxel as the next line of treatment after use of apalutamide. Use of genetic testing was reported in 36% of community physicians for newly diagnosed metastatic prostate cancer. CONCLUSIONS: There are several areas of community-based management of advanced prostate cancer that could represent potential areas for education, practice tools, and future research.

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC.

INTRODUCTION: Abiraterone acetate plus prednisone (AA+P) has shown to significantly improve survival. COSMiC, a Canadian Observational Study in Metastatic Cancer of the Prostate, set out to prospectively amass real-world data on metastatic castration-resistant prostate cancer (mCRPC) patients managed with AA+P in Canada. Herein, we report their patient-reported outcomes (PROs). METHODS: After a median followup of 67.1 weeks, 254 patients were enrolled across 39 sites. Functional Assessment of Cancer Therapy-Prostate (FACT-P), Montreal Cognitive Assessment (MoCA), Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), and Current Health Satisfaction in Prostate Cancer (CHS-PCa) were evaluated at baseline, as well as at weeks 12, 24, 48, and 72 after AA+P initiation. Descriptive analysis was used with continuous variables. Changes from baseline were summarized using mean (standard deviation [SD]). RESULTS: At a median age of 76.6 (8.94), baseline FACT-P total score was 111.3 (19.56) with no significant change in their functional status observed from baseline over time. The median baseline MoCA score was 25.2 (4.52), yet subsequent assessments showed an absence of cognitive decline while under treatment. Similarly, no meaningful changes were detected in BPI, BFI, and CHS-PCa during the 72-week study period, thus suggesting that patients' PROs were well-maintained throughout AA+P treatment. Prostate-specific antigen (PSA) response with >50% decline was 66.4%. Safety profile was consistent with the known side effect of AA+P. CONCLUSIONS: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real-world, prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study and underscores the importance of PRO use in this complex patient population.

Optimizing management of advanced urothelial carcinoma: A review of emerging therapies and biomarker-driven patient selection.

INTRODUCTION: Advanced urothelial carcinoma has been challenging to treat due to limited treatment options, poor response rates, and poor long-term survival. New treatment options hold the promise of improved outcomes for these patients. METHODS: A multidisciplinary working group drafted a management algorithm for advanced urothelial carcinoma using "consensus development conference" methodology. A targeted literature search identified new and emerging treatments for inclusion in the management algorithm. Published clinical data were considered during the algorithm development process, as well as the risks and benefits of the treatment options. Biomarkers to guide patient selection in clinical trials for new treatments were incorporated into the algorithm. RESULTS: The advanced urothelial carcinoma management algorithm includes newly approved first-line anti-programmed death receptor-1 (PD1)/ programmed death-ligand 1 (PD-L1) therapies, a newly approved anti-fibroblast growth factor receptors (FGFR) therapy, and an emerging anti-Nectin 4 therapy, which have had encouraging results in phase 2 trials for second-line and third-line therapy, respectively. This algorithm also incorporates suggestions for biomarker testing of PD-L1 expression and FGFR gene alterations. CONCLUSIONS: Newly approved and emerging therapies are starting to cover an unmet need for more treatment options, better response rates, and improved overall survival in advanced urothelial carcinoma. The management algorithm provides guidance on how to incorporate these new options, and their associated biomarkers, into clinical practice.

Management algorithms for metastatic prostate cancer.

INTRODUCTION: Prostate cancer poses a significant lifetime risk to Canadian men. Treatment for metastatic prostatic cancer (mPCa) is an area of ongoing research with a lack of up-to-date clinical guidance. The multidisciplinary Canadian Genitourinary Research Consortium (GURC) determined that additional guidance focusing on management of mPCa was warranted. METHODS: The most up-to-date guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining recommendations for the management of mPCa. RESULTS: A single pan-Canadian guideline and five national and international guidelines or consensus statements published since 2015 were identified, along with two new phase 3 trials and one additional randomized comparison. Iterative GURC discussions led to the development of two mPCa algorithms: the first addressing management of newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) patients and the second addressing treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). For newly diagnosed mCSPC patients with high-volume/high-risk disease, either docetaxel or abiraterone acetate and prednisone (AAP) added to androgen-deprivation therapy (ADT) is recommended. The addition of radiotherapy to ADT is suggested for those with low-volume disease and/or AAP to ADT for low-volume or low-risk disease. For first-line mCRPC, androgen receptor-axis-targeted (ARAT) therapy is recommended for most patients, while sequencing with docetaxel, radium-223, ARAT therapy, and/or cabazitaxel is recommended for later lines of therapy. CONCLUSIONS: Two treatment algorithms were developed for the management of mPC and can be used by multidisciplinary specialist teams to guide treatment.

Controversial issues in the management of patients with advanced prostate cancer: Results from a Canadian consensus forum.

INTRODUCTION: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. METHODS: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). RESULTS: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. CONCLUSIONS: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

Canadian Alzheimer's disease caregiver survey: baby-boomer caregivers and burden of care.

OBJECTIVE: Alzheimer's disease (AD) burdens not only the person, but also the person's caregiver(s). This burden has been linked to negative health effects for caregivers. To that end, a survey of Canadian caregivers of persons with AD/other dementias was conducted to investigate the social, physical, psychological and financial impact of AD and/or dementia-related conditions on caregivers' quality of life. METHODS: A web-based survey, the Canadian Alzheimer's Disease Caregiver survey, was made available through the Canadian Alzheimer's Society website and 50plus.com, an internet portal for baby boomers (BB) (people aged 50 years or older), as well as through HarrisDecima Research's e-Vox panel. A total of 398 individuals completed the survey between 15 September and 5 November 2006. RESULTS: Of the 398 total respondents, 221 were identified as baby boomers who provided care to an individual with AD/dementia. Respondents identified several areas of burden of care. These included negative effects on emotional health (such as increased depression, more stress and greater fatigue), financial costs and a need to change a working situation (e.g. by retiring early, reducing work hours or refusing a promotion). CONCLUSION: Caregivers of persons with AD/related dementia face important social, physical, psychological and financial pressures. These negatively affect the quality of life of caregivers with a significant increased burden being placed on live-in caregivers versus caregivers who do not co-reside with their care recipients. Interventions that address these pressures will not only improve the health and well-being of caregivers, but likely also the care of persons with AD/dementia.

Risperidone reduces aggression in boys with a disruptive behaviour disorder and below average intelligence quotient: analysis of two placebo-controlled randomized trials.

The present study aimed to analyse the effect of risperidone on a priori defined core aggression items. Data were pooled from 163 boys (aged 5-12 years, with or without comorbid attention-deficit/hyperactivity disorder) with a DSM-IV diagnosis of either conduct disorder or oppositional defiant disorder who had participated in either of two identical, 6-week, randomized, double-blind, placebo-controlled trials. All received treatment with either placebo or oral risperidone solution (0.01-0.06 mg/kg/day). Subjects had below average intelligence [intelligence quotient (IQ) 36-84] and a score of > or =24 on the Conduct Problem subscale of the Nisonger Child Behaviour Rating Form (N-CBRF). An expert advisory panel selected six core aggression items from the N-CBRF, from which a total Aggression Score (AS, range 0-18) was constructed. Compared to those treated with placebo, risperidone-treated subjects experienced significantly greater mean decreases from baseline in the AS at each of weeks 1-6 (P<0.001). By study endpoint, aggression among risperidone-treated subjects had declined by 56.4% (mean baseline AS 10.1; mean endpoint AS 4.4), which was more than twice that of placebo-treated subjects (mean baseline AS 10.6; mean endpoint AS 8.3; 21.7% reduction). Risperidone was efficacious in reducing symptoms of aggression in boys of below average IQ with disruptive behaviour disorders.