Trends in the use of novel hormonal agents at the end of life in metastatic castration-resistant prostate cancer.

40 Background: The approval of novel hormonal agents (NHAs), abiraterone and enzalutamide, have increased the therapeutic arsenal available in metastatic castration-resistant prostate cancer (mCRPC). However, the use of chemotherapy and other antineoplastics at the end of life has been suggested as an indicator of poor quality of care. In this study, we report the use of NHAs at the end of life in men with mCRPC in the province of Quebec, Canada. Methods: Using Quebec public healthcare administrative databases, we identified patients with prostate cancer who used an NHA (abiraterone or enzalutamide) after androgen deprivation therapy and who died between 2012 and 2016. The primary outcome was the use of an NHA in the 30 days before death. Use of an NHA in the 60 and 90 days before dying, and initiation (first prescription) of an NHA in the 30 days before death were evaluated as secondary outcomes. Multivariable analysis of the primary outcome was performed with logistic regression with results reported as odds ratios (OR) with 95% confidence intervals (95%CI). Results: The cohort consists of 1316 patients who used an NHA over the course of their disease and died at a median age of 78 years old, with 292 (22.2%), 464 (35.3%), and 575 (43.7%) having used an NHA in the 30, 60 and 90 days of life, respectively. Use of NHA 30 days before dying decreased over the study period, from 44.8% in 2012 to 17.0% in 2016 (Cochran-Armitage test p-value < 0.001). On multivariable analyses, later years of death remained associated with lower odds of NHA use 30 days before death (OR 0.74, 95%CI 0.66 to 0.81, p < 0.001). Fifty-eight (4.4%) patients initiated a NHA 30 days before dying. Conclusions: Rates of NHA use 30 days before dying were high initially but decreased over the study period. Further assessment of NHA use at the end of life is warranted to examine if the trend will be maintained given the recent approval of additional oral NHAs for prostate cancer.

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Clinical outcomes in Caucasian (C), African American (AA) and Asian men with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.186 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 186-186

Author(s):

Susan Halabi ◽

Sandipan Dutta ◽

Kim N. Chi ◽

Catherine M. Tangen ◽

Daniel Peter Petrylak ◽

...

Keyword(s):

Prostate Cancer ◽

African American ◽

Multivariable Analysis ◽

Phase Iii ◽

P Value ◽

Castration Resistant Prostate Cancer ◽

Risk Of Death ◽

Castration Resistant ◽

Hazard Ratios ◽

Asian Men

186 Background: We have previously shown in multivariable analysis that African American (AA) men had 19% lower risk of death than Caucasian (C) men with metastatic castration resistant prostate cancer (mCRPC) treated with a docetaxel (D) prednisone (P) based regimen. The primary goal of this analysis was to compare progression-free survival (PFS) and PSA PFS in C men, AA men, and Asian men with mCRPC treated with a DP based regimen. Methods: Individual patient data from 8,820 mCRPC men randomized on nine phase III trials to a DP containing regimen were combined. Race used in the analysis was based on self-report. The endpoints were PFS and PSA PFS. Per protocol definition of PFS was used in the analysis while PSA PFS was defined per PCWG3 criteria. The proportional hazards model was used to assess the prognostic importance of race in predicting PFS and PSA PFS, adjusting for treatment arm and prognostic factors that were common across the trials (performance status, and sites of metastases). Results: Of 8,820 patients, 7,528 (85%) were C, 500 (6%) were AA, 424 (5%) were Asian and 368 (4%) had race unspecified. Men with race unspecified were excluded from the analysis, leaving 8,452 men. Median PFS was 8.3 months (m) (95% CI = 8.1-8.5), 8.2 m (95% CI = 7.4-8.8), and 8.3 m (95% CI = 7.6-8.8) in C, AA and Asian men, respectively. In multivariable analysis adjusting for risk factors, the pooled hazard ratios for AA vs. C was 1.04 (95% CI = 0.94-1.15, p-value = 0.461) and 1.08 (95% CI = 0.96-1.21, p-value = 0.192) for Asian vs. C. PSA data were available for 6,685 (89%) C, 456 (91%) AA and 412 (97%) Asian men. Median PSA PFS were 9.7 m (95% CI = 9.4-10), 8.5 m (95% CI = 7.6-10) and 10.0 m (95% CI = 9.5-11.8) in C, AA and Asian, respectively. In multivariable analysis, the pooled hazard ratios were 1.05 (95% CI = 0.94-1.16, p-value = 0.408) for AA vs. C and 1.00 (95% CI = 0.82-1.22, p-value = 0.996) for Asian vs. C. Conclusions: There were no differences in PFS and PSA PFS outcomes in C, AA, or Asian men with mCRPC enrolled on these phase III clinical trials with DP. Clinical trial information: NCT00004001.

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Cancer Drug Use in the Last Month of Life in Men With Castration-Resistant Prostate Cancer

Journal of Oncology Practice ◽

10.1200/jop.18.00626 ◽

2019 ◽

Vol 15 (6) ◽

pp. e510-e519

Author(s):

Jason Hu ◽

Armen G. Aprikian ◽

Marie Vanhuyse ◽

Alice Dragomir

Keyword(s):

Prostate Cancer ◽

Targeted Therapy ◽

Drug Use ◽

End Of Life ◽

Administrative Databases ◽

Cancer Drug ◽

Castration Resistant Prostate Cancer ◽

Study Objective ◽

Castration Resistant ◽

Multivariable Analyses

PURPOSE: Several new drug therapies have been approved in CRPC in the past decade. However, little is known about their potential overuse at the end of life. Cancer therapy use at the end of life has been considered an indicator of overtreatment. The study objective was to describe CRPC drug use in the last month of life of CRPC patients in Quebec. PATIENTS AND METHODS: Using administrative databases from the province of Quebec in Canada, we identified patients who received medical or surgical castration treatment, received one or more CRPC drugs (chemotherapy, abiraterone, or bone-targeted therapy), and died between 2001 and 2013. CRPC drug use in the last month of life was the primary outcome. RESULTS: The cohort consisted of 1,148 patients with CRPC. A total of 316 men (27.5%) received a CRPC drug in the last month of life. For those who received chemotherapy, abiraterone, and bone-targeted therapy, 10.2%, 27.8%, and 31.8% received them in the last month of life, respectively. In multivariable analyses, age older than 75 years (odds ratio [OR], 0.75; 95% CI, 0.57 to 0.99), and prostate cancer diagnosis received less than 24 months earlier (OR, 0.43; 95% CI, 0.26 to 0.72) were associated with less CRPC drug use. Relative to dying between 2005 and 2011, dying between 2012 and 2013 (OR 1.60; 95% CI, 1.18 to 2.18) was associated with greater CRPC drug use. CONCLUSION: More than one quarter of patients received CRPC drug therapies in the last month of life. Persistent chemotherapy, abiraterone, bone-targeted therapies, and medical castration drugs in the last month of life may be an indicator of inappropriate and expensive end-of-life care.

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Comparative cardiotoxicity of the novel hormonal agents abiraterone and enzalutamide in metastatic castration-resistant prostate cancer using real-world data.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.62 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 62-62

Author(s):

Jason Hu ◽

Armen G. Aprikian ◽

Marie Vanhuyse ◽

Alice Dragomir

Keyword(s):

Prostate Cancer ◽

Heart Failure ◽

Clinical Trials ◽

Real World ◽

Administrative Databases ◽

Public Healthcare ◽

Castration Resistant Prostate Cancer ◽

Cardiovascular Risks ◽

The Real ◽

Castration Resistant

62 Background: Novel hormonal agents (NHAs) such abiraterone (ABI) and enzalutamide (ENZA) have demonstrated similar survival benefits against placebo groups in their respective clinical trials leading to their regulatory approval in both the pre- and post-chemotherapy settings in metastatic castration-resistant prostate cancer (mCRPC). Despite the overall tolerable risk profile, certain signals of cardiovascular toxicity were reported for these agents in clinical trials but little is known about their incidence in clinical practice. The objective was to assess the comparative cardiovascular safety of ABI and ENZA in patients with mCRPC in the real-world. Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. Patients were selected on the basis of having received androgen deprivation therapy prior to initiating a novel hormonal agent (ABI or ENZA) between 2012 and 2016. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary disease, cerebrovascular disease, heart failure, arrhythmia and other cardiovascular causes). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline confounders including pre-existing cardiovascular disease. Results: The cohort comprises 2,183 patients, with 1,773 (81.2%) in the ABI group and 410 (18.8%) in the ENZA group. Before IPTW, mean age of the ENZA group was higher than the ABI group (78 vs 76). There were more ENZA patients with pre-existing arrythmia (ABI: 10.7%, ENZA: 15.1%) and diabetes (ABI: 21.5%, ENZA: 25.1%). Crude incidence rates of cardiovascular-related hospitalization were of 10 events per 100 person-years (PYs) and of 7 events per 100 PYs for the ABI and ENZA groups, respectively. After applying IPTW, all baseline variables were well balanced across both groups with standardized differences < 0.05. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZA group (IPTW-hazard ratio (HR): 1.79, 95% confidence interval (95%CI): 1.04-3.09). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR: 3.02, 95%CI: 1.17-7.78). Conclusions: In our study population, there was a greater risk of cardiovascular-related hospitalizations for ABI users relative to ENZA users, in particular for hospitalization for heart failure. Given the lack of evidence from randomized head-to-head comparisons of both agents, these results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.

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Clinical Variables Associated with PSA Response to Lutetium-177-PSMA ([177Lu]-PSMA-617) Radionuclide Treatment in Men with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽

10.3390/cancers12051078 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1078

Author(s):

Moran Gadot ◽

Tima Davidson ◽

Margalit Aharon ◽

Eshetu G. Atenafu ◽

Avraham Malki ◽

...

Keyword(s):

Prostate Cancer ◽

Logistic Regression ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Real Life ◽

Categorical Variables ◽

P Value ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Psa Response

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan–Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ2/Fisher’s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the ‘real-life’ setting of heavily pretreated men with mCRPC.

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Treatment Given Near the End of Life in Castration-Resistant Prostate Cancer

American Journal of Hospice and Palliative Medicine® ◽

10.1177/1049909111433128 ◽

2012 ◽

Vol 29 (7) ◽

pp. 536-540 ◽

Cited By ~ 3

Author(s):

Hanna A. Zaghloul ◽

Jose R. Murillo

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

End Of Life ◽

Treatment Options ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Related Quality ◽

Impact On Survival ◽

New Treatments

Chemotherapy treatment options are limited for patients with castration-resistant prostate cancer (CRPC). The purpose of this study is to report treatment use and adverse effects (AEs) within the last three months of life in patients with CRPC. Of the 88 patients identified, 32% received treatment within 3 months of death, and documented AEs occurred in 25% of patients. Of those, neutropenia (18.3%), nausea/vomiting (18.3%), and febrile neutropenia (13.6%) were the most frequent. Results of this study show high treatment utility towards the end-of-life in patients with CRPC, with one fourth of patients experiencing AEs. Attention to health-related quality of life becomes increasingly important as new treatments appear to have small impact on survival, and AEs of those treatments may significantly impact patient quality of life.

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Use of New Therapies and Hospital Admission Near the End of Life in Castration Resistant Prostate Cancer (CRPC) in the Castration Resistant Prostate Cancer Registry (CAPRI) in the Netherlands

Value in Health ◽

10.1016/j.jval.2017.08.009 ◽

2017 ◽

Vol 20 (9) ◽

pp. A400

Author(s):

M Kuppen ◽

H Westgeest ◽

A Van den Eertwegh ◽

W Gerritsen ◽

C Uyl - de Groot

Keyword(s):

Prostate Cancer ◽

The Netherlands ◽

Hospital Admission ◽

End Of Life ◽

Cancer Registry ◽

Castration Resistant Prostate Cancer ◽

New Therapies ◽

Castration Resistant

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Efficacy of docetaxel and androgen receptor axis-targeted agents in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.150 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 150-150

Author(s):

Akiyuki Yamamoto ◽

Masashi Kato ◽

Toyonori Tsuzuki ◽

Momokazu Gotoh

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Primary Outcome ◽

Progression Free Survival ◽

Intraductal Carcinoma ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

Carcinoma Of The Prostate ◽

Castration Resistant ◽

Time Of Administration

150 Background: This study aimed to investigate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P). Methods: We retrospectively identified 311 CRPC patients from June 2002 to February 2016. All patients were initially administered with androgen deprivation therapy (ADT), followed by docetaxel or ARAT (abiraterone or enzalutamide) after progressing to CRPC. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis and progression-free survival (PFS) from the time of administration of docetaxel or ARAT. Results: IDC-P was found in 180 of 311 patients. The median OS was 33.4 and 64.0 months with and without IDC-P, respectively (hazards ratio [HR], 2.14; P < 0.001). For the first treatment for CRPC, docetaxel was administered to 71 and 50 patients with and without IDC-P, respectively, with a median OS of 30.4 and 64.0 months, respectively (HR, 2.62; P < 0.001). ARAT was administered to 109 and 81 patients with and without IDC-P, respectively, with a median OS of 45.0 and 69.9 months, respectively (HR, 1.84; P = 0.017). Regarding patients with IDC-P, the OS in patients who were administered with ARAT was longer than that in those administered with docetaxel (HR, 0.58; P = 0.008). The median PFS was 7.5 and 12.1 months with and without IDC-P, respectively (HR, 1.36; P = 0.03). Multivariate analysis showed that the prognostic factors for OS were the presence of IDC-P (HR, 1.91; P < 0.001), and administration of ARAT (HR, 0.66; P = 0.02). Conclusions: The presence of IDC-P is an independent prognostic factor for OS and PFS in CRPC patients. ARAT may prolong OS in CRPC patients with IDC-P.

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