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.

Patterns of care for non-metastatic castration-resistant prostate cancer: A population-based study.

Objectives: To describe patterns of practice of PSA testing and imaging for Ontario men receiving continuous ADT for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). Patients and Methods: This was a retrospective, longitudinal, population-based study of administrative health data from 2008 to 2019. Men 65 years and older receiving continuous androgen deprivation therapy (ADT) with documented CRPC were included. An administrative proxy definition was applied to capture patients with nmCRPC and excluded those with metastatic disease. Patients were indexed upon progression to CRPC and were followed until death or end of study period to assess frequency of monitoring with PSA tests and conventional imaging. A 2-year look-back window was used to assess patterns of care leading up to CRPC as well as baseline covariates. Results: At a median follow-up of 40.1 months, 944 patients with nmCRPC were identified. Their median time from initiation of continuous ADT to CRPC was 26.0 months. 60.7% of patients had their PSA measured twice or fewer in the year prior to index, and 70.7% patients did not receive any imaging in the year following progression to CRPC. Throughout the study period, 921/944 (97.6%) patients with CRPC progressed to high-risk (HR-CRPC) with PSA doubling time ≤ 10 months, of which more than half received fewer than three PSA tests in the year prior to developing HR-CRPC, and 30.9% received no imaging in the subsequent year. Conclusion: PSA testing and imaging studies are underutilized in a real-world setting for the management of nmCRPC, including those at high risk of developing metastatic disease. Infrequent monitoring impedes proper risk stratification, disease staging and detection of treatment failure and/or metastases, thereby delaying the necessary treatment intensification with life-prolonging therapies. Adherence to guideline recommendations and the importance of timely staging should be reinforced to optimize patient outcomes.

Real-world use of systemic therapies in men with metastatic castration resistant prostate cancer (mCRPC) in Canada.

BACKGROUND: Management of advanced prostate cancer has evolved rapidly with the availability of multiple systemic treatments such as androgen-receptor axis-targeted therapies (ARATs), taxane-based chemotherapy, radium-223, and other approaches. However, limited data exists on real-world treatment selection and clinical outcomes. This study examines the utilization and survival impact of these therapies in men with metastatic castration-resistant prostate cancer (mCRPC) in the real-world setting of Ontario, Canada. METHODS: This study was a retrospective, longitudinal, population-based study of administrative claims data between January 2016 and April 2020. Men ≥ 66 years with mCRPC receiving advanced treatment were included. Patients were indexed on the day they initiated mCRPC treatment and followed up until death or end of study period to assess treatment and survival. Multinomial regression was used to model the association between baseline covariates, treatment and survival. RESULTS: Median age was 75 years among the 944 mCRPC patients who received life-prolonging therapies during this time period. Over 90% of patients used an ARAT as a first-line therapy, and 71.5% received only first-line therapy before death or censoring. Of patients that received two or more lines, over 80% received subsequent therapy with a different mechanism of action. Median overall survival was 18.9 months. CONCLUSIONS: ARATs have become the predominant first-line systemic treatment option for mCRPC patients in recent years. Notably, the majority of patients received only a single line of life-prolonging therapy after developing mCRPC. In keeping with the recognized efficacy-effectiveness gap, real-world outcomes in this cohort appear poorer than in clinical trials.

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.

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.

The Influence of the Evolution of First-Line Chemotherapy on Steadily Improving Survival in Advanced Non-Small-Cell Lung Cancer Clinical Trials.

Over the past three decades, survival in advanced non-small-cell lung cancer (NSCLC) clinical trials has doubled with an increase in 1-year survival from 25% to 50 to 55%. This has been mainly attributed to improvements in systemic therapy. Although modern first-line chemotherapy regimens have more favorable toxicity profiles, a statistically significant improvement in overall survival has not been demonstrated in existing meta-analyses of second-generation versus third-generation combinations. Moreover, pivotal trials demonstrating statistically significant survival superiority of third-generation regimens are consistently not reproducible even for nonsquamous populations using pemetrexed-platinum combinations. As enhancement in the efficacy of first-line systemic therapy in patients without identifiable driver mutations is questionable, other factors are discussed that explain the doubling of 1-year survival reported in clinical trials. These factors include second-line or third-line therapy, maintenance chemotherapy, performance status selection, stage migration, sex migration, improved treatment of brain metastases, and better palliative care.

Outcomes of patients treated with capecitabine and temozolamide for advanced pancreatic neuroendocrine tumors (PNETs) and non-PNETs.

BACKGROUND: Retrospective studies have demonstrated high response rates among patients with advanced pancreatic neuroendocrine tumors (PNETs) treated with capecitabine and temozolamide (CapTem), while responses are infrequently seen among non-PNETs. The objective of the study was to describe progression free survival (PFS) among neuroendocrine tumor (NET) patients treated with CapTem, and to identify factors associated with better activity. METHODS: Patients who were referred to one of five provincial cancer treatment centers between 2009 and 2013 for advanced NETs and initiated CapTem were included. Patients received Cap 1,500 mg/m(2) on days 1-14 and TMZ 200 mg/m(2) on days 10-14 every 28 days. Their characteristics and outcomes were retrospectively analyzed. RESULTS: In our cohort, 29 patients (16 males) with a median age of 59 (range 26-76) received palliative CapTem, 15 of them as first-line chemotherapy. Primary tumors included pancreas (48.3%), small bowel (20.7%), lung (10.3%), unknown (10.3%), rectum (6.9%) and appendix (3.4%). Median number of cycles was three. Fifteen patients (51.7%) received CapTem as first-line chemotherapy and 14 (48.3%) as subsequent lines. Median PFS for the entire cohort was 4.7 months. PNETs had a median PFS of 4.9 months compared to 2.8 months for non-PNETs (P=0.178). Patients with PNETs who received CapTem in the first-line setting had a median PFS of 15.9 months as compared to only 3.1 months for the remainder [P=0.047, hazard ratios (HR) 0.342]. Patients with Ki67 above 5% and ≤5% had median PFS of 4.0 and 4.7 months, respectively (P=0.260). CONCLUSIONS: CapTem showed good activity among PNETs, but its broader role in the treatment of carcinoid tumors remains unclear.