Evaluating the effect of therapy duration on survival in patients with metastatic castration-resistant prostate cancer receiving radium-223.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e593-e593
Author(s):  
Noelle L. Williams ◽  
Kamila Nowak-Choi ◽  
Jenna Skowronski ◽  
Tu Dan ◽  
Harriet Belding Eldredge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Second Generation ◽  
Cox Regression ◽  
Rank Test ◽  
Maximal Effect ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Full Treatment ◽  
Radium 223

e593 Background: The use of radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC) improves overall survival (OS) and quality of life. Combination of radium-223 with second-generation anti-androgens has further improved OS; however, the optimal length of radium-223 treatment for maximal effect remains unknown. Methods: We reviewed 35 consecutive patients with mCRPC who received radium-223 from December 2012 to August 2015 at Thomas Jefferson University. Patients were divided into two groups: those who received full treatment of 6 injections (n = 18) versus those who received less than 6 injections (n = 17). Kaplan-Meier analysis of OS were tested for difference by treatment group using Log Rank test. Univariable association with survival outcomes was calculated with univariable Cox regression and Log Rank tests. Results: Mean age was 73 ± 10 years and Karnofsky performance status (KPS) ranged from 50-90 (median, 80). Median follow-up was 13.9 months. Eighteen patients were receiving concurrent second generation anti-androgens at the start of treatment. Median OS was 12 months for patients who received 6 injections and 6.48 months for patients who received less than 6 injections (p = 0.0045). The results of univariate Cox regression analysis revealed full treatment was associated with increased OS (p = 0.0013). On multivariate analysis accounting for KPS, full treatment was significantly associated with improved OS (p = 0.0028). Conclusions: In this retrospective, single-institution analysis, we demonstrated that full course completion of radium-223 was associated with improved OS in patients with mCRPC. These patients should be optimally supported during treatment to allow for therapy completion.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

A meta-analysis on individual data of bone-targeting radio-isotopes in men with bone metastases from castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 352-352
Author(s):  
Safae Aarab Terrisse ◽  
Chris C. Parker ◽  
Karamouza Eleni ◽  
A. Oliver Sartor ◽  
Nicholas James ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Meta Analysis ◽  
External Beam Radiotherapy ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Significant Difference ◽  
Radio Isotopes

352 Background: Among bone-targeted radio-isotopes (RI), Radium-223 (an α-emitter) is the only one with clearly demonstrated overall survival (OS) benefit in men with castration-resistant prostate cancer (CRPC). The aim of this meta-analysis is to estimate the OS impact of RI in men with CRPC. Methods: An individual patient data meta-analysis was carried out from randomized trials with inclusion period 1993-2013. Eligible trials included more than 50 patients, mandated bone metastases from CRPC and randomly evaluated RI. Endpoints were OS (primary), symptomatic skeletal events (SSE) and toxicity. A fixed-effect model was used. The log-rank test stratified by trial was used to estimate individual and overall hazard ratios (HR). Subset analyses were performed by the type of radiation (α vs. β emission) and by trial comparison: RI + Chemotherapy (CT) vs. CT, RI+ External beam radiotherapy (EBRT) vs. EBRT, RI vs. EBRT. Results: From 9 identified trials, data from 6 trials comprising 2081 patients (min: 64, max: 921) were collected with 2 trials representing 80% of data. The data from 3 trials (n = 341) were not available. The overall effect on OS favoured RI with HR = 0.86 [0.77-0.95] but high heterogeneity between trials (p < 0.001, I2= 79.6%). The overall effect of α- emitters on OS (HR = 0.70 [0.58; 0.83], 2 trials, n = 985) significantly differed from that of β-emitters (HR = 0.96 [0.84; 1.10], n = 4 trials, n = 1096) (interaction p = 0.0041). The overall effect on SSE favoured RI with HR = 0.81 [0.69-0.93] (4 trials, n = 1806) with marked between trial heterogeneity (p = 0.08, I² = 55.3%) and a significant difference (p = 0.02) by the type of RI (α-emitters: HR = 0.65 [0.52-0.82]-2 trials, β-emitters: HR = 0.93 [0.77-1.13]-2 trials). Conclusions: In men with metastatic CRPC a significant improvement of OS and SSE was obtained with bone targeted α-emitter radio isotopes, but not with β-emitter. However, some between trial heterogeneity of effects on OS need further investigations.

scholarly journals Treatment-Emergent Co-Morbidities and Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Abiraterone or Enzalutamide

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Ting Lin ◽  
Yen-Chun Huang ◽  
Chih-Kuan Liu ◽  
Tian-Shyug Lee ◽  
Mingchih Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Hormone Therapy ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Drug Induced ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Significant Difference ◽  
Taiwan National Health Insurance

Secondary hormone therapy, abiraterone and enzalutamide, has improved outcomes for metastatic castration-resistant prostate cancer (mCRPC) and prolonged patients’ lives significantly. Various studies have compared the cancer-related outcomes, adverse effects, and drug-induced comorbidities in patients with mCRPC who are treated with abiraterone or enzalutamide. However, few studies have explored associations between survival and comorbidities or comprehensive analyzed newly developed comorbidities during and after secondary hormone therapy. We attempted to clarify whether the Charlson comorbidity index (CCI) overall or itemized is predictive for overall survival, and we compared newly developed comorbidities between abiraterone and enzalutamide groups. We extracted data about expenses and comorbidities for patients who have mCRPC, received abiraterone and enzalutamide and met pre-examination operation criteria between September 2016 and December 2017 from the Taiwan National Health Insurance database. A total of 1153 patients with mCRPC who received abiraterone (n = 782) or enzalutamide (n = 371) with or without previous chemotherapy were included. We used the propensity score to match confounding factors, including age, pre-existing comorbidities, and precipitating factors for comorbidity (e.g., hypertension, hyperlipidemia), to eliminate selection bias in the comparison of newly developed comorbidities. Cox regression analysis was used for overall survival. We found that enzalutamide is superior to abiraterone with regard to overall survival. Our study revealed that there is no statistically significant difference in development of new comorbidities between abiraterone and enzalutamide group. Moreover, the CCI score, rather than any single item of the CCI, was a statistically significant predictor for overall survival.

Comparison of enzalutamide versus abiraterone in castration-resistant prostate cancer before docetaxel: Results of a propensity score-matched analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16540-e16540
Author(s):  
Marcelle Goldner Cesca ◽  
Maysa Tamara Silveira ◽  
Natasha Carvalho Pandolfi ◽  
Thiago Bueno Oliveira ◽  
José Augusto Rinck ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Propensity Score ◽  
Cox Regression ◽  
Primary Objective ◽  
Rank Test ◽  
Cancer Center ◽  
Matched Cohort ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response

e16540 Background: Metastatic castration-resistant prostate cancer (mCRPC) phenotype involves androgen-receptor signalling mechanisms that support the use of enzalutamide (EZ) and abiraterone (Abi). These therapies improve overall survival (OS) and quality-of-life, with a favourable safety profile. There is no validated data defining the best drug or sequence to be used. Methods: A retrospective cohort of mCRPC patients (pts) was analysed at AC Camargo Cancer Center. The primary objective was to compare progression-free survival (PFS) and OS in patients treated with EZ or Abi as first line (docetaxel naïve pts). Kaplan-Meier, Log-Rank Test and Cox Regression were used for survival analysis. To address unbalanced characteristics between the two treatment groups treatment efficacy was compared in a propensity score matched cohort. Results: From May, 2002 to September, 2017, 120 pts were treated with Abi (84%) or EZ (36%). Median follow-up was 21.2 months. Median age at diagnosis was 66 (48-84), the majority were Gleason score 7 (34%) and median baseline PSA was 14. Median PFS was 17.4 months in EZ and 10.6 months in Abi group (HR = 0.65; 95%CI: 0.39-1.10; p = 0.11). Median OS was not reached and 31.6 months for EZ and Abi, respectively (HR = 0.60; 95%CI: 0.27-1.36; p = 0.22). EZ was associated with a better PSA response in the first 4 months of treatment (p < 0.001). Independent prognostic factors for worse OS and PFS were ECOG ≥ 1, treatment toxicity ≥ G1 and lower PSA doubling time before treatment and for better OS and PFS were PSA response in the first 4 months and alkaline phosphatase and lactate dehydrogenase response at any time. In the propensity score matched cohort including 72 patients PFS was better in EZ group (HR = 0.36; 95%CI: 0.20-0.64; p < 0.001) but there was no difference in OS (HR = 0.66; 95%CI: 0.27-1.63; p = 0.37). Conclusions: EZ was associated with prolonged PFS and better PSA response, with no OS improvement when compared with Abi for mCRPC before docetaxel, in a propensity score matched analysis.

Prediction of favorable outcome in a docetaxel rechallenge setting in metastatic castration-resistant prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 68-68
Author(s):  
Matthias Michael Heck ◽  
Mark K. Thalgott ◽  
Margitta Retz ◽  
Petra Wolf ◽  
Tobias Maurer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Oncological Outcome ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Treatment Variable ◽  
Castration Resistant ◽  
Line Chemotherapy

68 Background: To identify predictors of favourable oncological outcome in metastatic castration-resistant prostate cancer (mCRPC) patients who are treated with docetaxel rechallenge following first-line chemotherapy with docetaxel. Methods: We retrospectively evaluated the oncological outcome of mCRPC patients who were treated with 3-weekly docetaxel (75mg/m2) at first-line chemotherapy and rechallenge plus prednisone/ prednisolone. The endpoints of oncological outcome were PSA-progression-free survival (PSA-PFS) and overall survival (OS) after initiation of docetaxel rechallenge. The effect of clinical variables on PSA-PFS and OS was statistically analysed by a log-rank test or Cox regression with hazard ratios. All analyses were performed using a 0.05 level of significance. Results: 47 patients were included on analysis. At a median follow-up of 25.8 months (range 9.8-89.8 months) after the first administration of docetaxel, 27 (57.4%) patients had died. Median PSA-PFS was 5.9 months (95% CI 3.5-6.8 months) and median OS was 21.4 months (95% CI 18.9-23.9 months) after initiation of docetaxel rechallenge. PSA-reduction ≥ 30% was the only pre-treatment variable that correlated significantly with prolonged PSA-PFS (p=0.03) and OS (p=0.002). Patients with PSA-reduction ≥ 30% at first-line chemotherapy showed a median OS of 21.8 months since initiation of docetaxel rechallenge in comparison to 4.5 months in patients with < 30% PSA-reduction. Conclusions: Docetaxel rechallenge represents an active treatment option in selected docetaxel-pretreated patients with mCRPC. In this retrospective study, PSA-reduction ≥ 30% at first-line chemotherapy with docetaxel predicted superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.

scholarly journals Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study

2020 ◽  
Vol 66 (6) ◽  
pp. 842-851
Author(s):  
Guillemette E Benoist ◽  
Inge M van Oort ◽  
Emmy Boerrigter ◽  
Gerald W Verhaegh ◽  
Onno van Hooij ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Observational Study ◽  
Prognostic Value ◽  
Cox Regression ◽  
Response To Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Cox Regression Analysis ◽  
Castration Resistant

Abstract Background Several treatment options were recently added for metastatic castration-resistant prostate cancer (mCRPC). However, response to therapy is variable, and biomarkers that can guide treatment selection and response evaluation are lacking. Circulating RNAs are a promising source of biomarkers. We explored messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) as potential biomarkers in liquid biopsies of patients with mCRPC treated with enzalutamide. Methods Forty patients were included in this prospective multicenter observational study. Whole blood was drawn at baseline and 1, 3, and 6 months after start of therapy. Four mRNAs, 6 miRNAs, and 5 lncRNAs were analyzed by quantitative PCR. RNA levels in 30 healthy individuals were used as controls. RNA expression data were analyzed by Kaplan–Meier and Cox regression analyses, and the primary end point was progression-free survival. Clinical factors were included in the multivariable Cox regression analysis. Results Levels of 2 miRNAs, miR-375 and miR-3687, and 1 lncRNA, N-acetylated alpha-linked acidic dipeptidase like 2 antisense RNA 2 (NAALADL2-AS2), were more than 2-fold higher in patients with mCRPC compared with healthy volunteers. Patients with higher levels of miR-375 or miR-3687 showed a shorter time to progression. Patients with higher levels of NAALADL2-AS2 showed a longer time to progression. In the multivariable Cox regression analysis, higher miR-375, miR-3687 and serum prostate-specific antigen concentrations were shown to be independent predictors for shorter time to progression. Conclusions We identified miR-3687 as a novel prognostic marker for response in patients with CRPC treated with enzalutamide, and we confirmed the prognostic value of miR-375.

scholarly journals Radium-223 in a Community Setting for Castration Resistant Prostate Cancer

2017 ◽  
Vol 6 (1) ◽  
pp. 44
Author(s):  
Houman Vaghefi ◽  
Sachin Agarwal ◽  
Fang Liu ◽  
Bide Xiong ◽  
Elizabeth Garber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Survival ◽  
Treatment Effectiveness ◽  
Community Setting ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Cancer Trial ◽  
Castration Resistant ◽  
Radium 223 ◽  
Signed Rank Test

Purpose: To evaluate the toxicity, palliative benefit, and survival benefit of Radium-223 (Ra-223) in a community setting.Introduction: The ALSYMCA (Alpharadin in Symptomatic Prostate Cancer) trial demonstrated improved survival for men with painful bone metastasis from castration resistant prostate cancer who were treated with Ra-223. The median survival was 14.9 months for the Ra-223 patients compared to 11.3 months for patients treated with a placebo.Methods: We identified through the nuclear medicine records 11 patients who started Ra-223 between March 15, 2013 and December 10, 2015. The Wilcoxon signed rank test was used to compare the published results of the ALSYMPCA patients with those from our institution.Results: The Hodges-Lehman estimate of the median survival of our patients from the date of the first Ra-223 infusion was 7.8 months. The 95% confidence interval (CI) was (2.8, 14.7; p=0.0122) indicating our patients had a significantly shorter survival than the Ra-223 ALSYMPCA patients.Our patients did not have a statistically significant worse rate of anemia, neutropenia, or thrombocytopenia. We used 3 measures of treatment effectiveness: 1) reduction in the pain scores, 2) reduction in the serum PSA, and 3) reduction in the alkaline phosphatase from baseline, but the reductions were not statistically significant.Conclusions: This small study is not meant to challenge the results of the ALSYMPCA international trial. It is intended only as a caution that prior lines of therapy, especially with newer agents such as abiraterone and enzalutamide, may attenuate the benefit from this treatment, particularly in elderly patients.Radium-223 in a Community Setting for Castration Resistant Prostate Cancer

scholarly journals Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

2021 ◽  
Author(s):  
Maarten J. van der Doelen ◽  
Agnes Stockhaus ◽  
Yuanjun Ma ◽  
Niven Mehra ◽  
Jeffrey Yachnin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alkaline Phosphatase ◽  
Confidence Interval ◽  
Surrogate Marker ◽  
Response Monitoring ◽  
Castration Resistant Prostate Cancer ◽  
Related Event ◽  
Castration Resistant ◽  
Radium 223 ◽  
Skeletal Related Event

Abstract Purpose Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). Methods This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. Results A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5–15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73–3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. Conclusion Early treatment–induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

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