The National Radium-223 Dichloride Audit group: Data from patients in UK oncology centers with metastatic castration-resistant prostate cancer treated with radium-223 dichloride.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Manreet Randhawa ◽  
Robert J Jones ◽  
Irene Stratton ◽  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Univariate Analysis ◽  
Routine Care ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Laboratory Parameters ◽  
Castration Resistant ◽  
Radium 223 ◽  
The Uk

e16524 Background: Clinicians in 17 UK oncology centres comprise the National Radium-223 Dichloride Audit (NRDA) group which is evaluating treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride (Xofigo). Methods: Patients commencing treatment from 1st September 2017 were included. Clinical and laboratory parameters were collected throughout treatment. Analyses used frequency tables and univariate analysis. Results: As of February 2019, data from 400 patients has been collected. We report the outcomes on the first 150 patients who are evaluable. At first treatment, median age was 72 years (25th to 75th centile: 67-78), 54% of patients had an ECOG performance status (PS) of 1, 32.6% of patients had a WHO pain score of 1, 60% of patients had an ALP level of < 220U/L and 26% of patients received docetaxel for mCRPC. The mean number of cycles completed was 5. Sixty patients (40%) did not complete 6 cycles and 42/60 (70%) discontinued due to disease progression. Changes in variables between treatment 1 and 6 are shown in Table. Adverse events reported were fatigue (76%), diarrhoea (38%), nausea/vomiting (35%), constipation (32%), anaemia (28%), thrombocytopaenia (12%) and neutropaenia (5%). There was no overall change in ECOG PS. In those who completed quality of life (QOL) questionnaires at treatment 1 and 6 (58%), there was no difference. Conclusions: The ongoing NRDA Group records data from mCRPC patients treated across the UK in routine care. To our knowledge, it is the first prospective analysis of such patients and the largest in assessing treatment patterns and outcomes including QOL data as well as standard laboratory parameters. Disclosures: The NRDA Group has been funded by a research grant from Bayer.[Table: see text]

Abiraterone acetate (AA) with or without cabazitaxel (CBZ) in treatment of chemotherapy naive metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 84-84
Author(s):  
Susan F. Slovin ◽  
Karen E. Knudsen ◽  
Susan Halabi ◽  
Mark T. Fleming ◽  
Ana M. Molina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Networks ◽  
Radiographic Progression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant

84 Background: Loss of retinoblastoma tumor suppressor (RB) function has been shown to lead to CRPC and is strongly associated with poor outcome. RB functions as a transcriptional repressor; as such, loss of RB causes de-repression of pro-tumorigenic gene networks, including deregulation of the androgen receptor (AR) locus, excessive AR production, and castration-resistant (ligand independent) AR activity that can bypass hormone therapy. Our hypothesis is that leveraging RB status can direct treatment decisions. The primary objective of the trial (NCT02218606) was to determine the radiographic progression free survival (rPFS) of AA/prednisone (AAP) with and without CBZ in mCRPC patients (pts) that have progressed on primary androgen deprivation therapy and no prior AR directed therapy or chemotherapy. Methods: This is a multicenter non-comparative randomized phase 2 trial. Pts were randomized 1:1 to AAP with crossover to CBZ upon AAP failure (Arm 1), or the combination of AAP + CBZ (Arm 2). Randomization was stratified by the CALGB 90401 prognostic risk groups. The primary endpoint was rPFS (time from randomization to radiographic progression or death, whichever occurs first). Arms were analyzed separately. Results: Between October 2014 and March 2019, 93 pts were accrued; 81 were randomized. Median age was 68 years and ECOG performance status was 0 or 1. Endpoints are shown in Table. Therapies were well tolerated. Conclusions: Results of AAP + CBZ (Arm 2) in chemotherapy naïve pts suggest that men may derive benefit from the earlier use of CBZ with acceptable toxicity, supporting further study of this combination in mCRPC pts. Circulating Tumor Cells are being analyzed for changes in RB/AR expression. Managed by: Prostate Cancer Clinical Trials Consortium; Funding: Sanofi US; Support: Prostate Cancer Foundation. Clinical trial information: NCT02218606. [Table: see text]

Integration of radium-223 dichloride (Xofigo) into clinical practice for the treatment of castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 312-312
Author(s):  
Catherine Mary Doyle ◽  
Matthew Mills ◽  
Sultan Damgaci ◽  
Johnna Smith ◽  
Jingsong Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Bone Metastases ◽  
Univariate Analysis ◽  
Treatment Completion ◽  
Categorical Variables ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Complete Treatment

312 Background: Radium-223 dichloride (Xofigo) is an FDA-approved radionuclide used to treat symptomatic bone metastases in patients with castration-resistant prostate cancer (CRPC) with no known visceral metastases. Outside of clinical trial, the benefits of Radium-223 dichloride (Ra-223) in the treatment of CRPC have not yet been fully delineated in real life setting. Therefore, the purpose of this study was to evaluate the outcome of patients with CRPC who were treated with Ra-223, especially studying the variables associated with completion of 6 cycles of therapy. Methods: A total of 114 patients with CRPC and bone metastases referred for treatment with Ra-223 between March 2010 and February 2018 were identified for retrospective analysis. A chart review was conducted to analyze clinical characteristics, treatments, and outcomes including radiologic bone scans. Categorical variables were compared using Chi-square and independent student t test, and survival rates were generated using Kaplan-Meier analysis. Multivariate analysis (MVA) Cox proportional hazard ratios (HR) model was used in the assessment of OS and PFS. Results: Of the 114 patients referred for treatment, the overall median OS was 12.6 months. In MVA, improved OS was most strongly associated with completion of all six doses (p < 0.001). Median OS for the 56 patients who received full treatment was 24 months, while median OS for the 107 patients who did not complete treatment was 5.9 months. In univariate analysis, treatment completion was significantly associated with prior Sipuleucel-T (p = 0.002), concurrent Denosumab (p = 0.027), and baseline PSA < 30 ng/mL (p = 0.004). Conclusions: Completion of treatment with Ra-223 is a significant factor associated with improved OS. Therefore it is clinically important to delineate which patients are to the most appropriate candidates to complete treatment. Factors notable for treatment completion suggest patients might benefit from initiating Ra-223 treatment after receiving Sipuleucel-T and while their PSA remains low. Further consideration should be given to the sequence of Ra-223 in clinical practice, including use of concurrent Abiraterone and Enzalutamide.

The National Radium-223 Dichloride Audit Group: Data from patients in United Kingdom oncology centers with metastatic castration-resistant prostate cancer treated with radium-223 dichloride.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 59-59
Author(s):  
Manreet Randhawa ◽  
Irene Stratton ◽  
Robert J. Jones ◽  
Keyword(s):  
Prostate Cancer ◽  
Final Analysis ◽  
Outcome Data ◽  
Treatment Patterns ◽  
Quality Data ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
The Uk ◽  
Ecog Ps

59 Background: Clinicians in 20 UK oncology centres comprise the National Radium-223 Dichloride Audit group which is evaluating treatment patterns and outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with Radium-223 dichloride (Xofigo). Methods: Pts first treated with Xofigo from September 2017 were included and demographics, treatment, clinical, biochemical and outcome data collected prospectively. Analysis was carried out using frequency tables, univariate and survival analysis. Results: We report the outcomes on the first 100 pts in 4 centres with good quality data. Median values of each characteristic including 25th and 75th percentiles are as follows: Age at diagnosis = 67 years (62-72), weight = 83.5kgs (73.6-92.8), Hb = 139g/L (118 – 136), WCC = 7.3X109/L (5.7 – 8.7), plt count = 252x109/L (208 – 290), ALP = 128U/L (96-263) and PSA = 42.1ug/L (21.5 – 125.7). A majority of pts had an ECOG PS of 0-1. The number of pts having Xofigo as 1st, 2nd, 3rd and 4th line treatment was 15, 64, 20 and 1 respectively. There was a statistically significant decline in median weight, Hb, WCC, plt count and ALP and a rise in PSA between cycle 1 and cycle 6. Thirty eight pts did not complete 6 cycles with 31 of these (82%) discontinuing due to disease progression. The prevalence of adverse events was 5% (20/100). Twenty nine pts had a skeletal event by 12 months. There was no change in the WHO analgesic score, QOL scores or ECOG PS between treatment 1 and 6. Thirty nine pts had subsequent lines of treatment with 31 of these having only 1 line of treatment. Median overall survival was 363 days (95% CI 312-426 days). Conclusions: The ongoing National Radium-223 Dichloride Audit records data from approximately 600 mCRPC pts treated across the UK in routine clinical NHS care. To our knowledge, it is the first prospective analysis of such pts and the largest in assessing treatment patterns, outcomes and quality of life data in addition to standard biochemical and clinical parameters. Further multivariate analysis will be presented and the implications of the licensing change of Xofigo will be illustrated in the final analysis.

scholarly journals A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration resistant prostate cancer

2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
Study Results

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

2020 ◽  
pp. 107815522095161
Author(s):  
Özgecan Dülgar ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Seval Ay ◽  
Deniz Tural ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
One Year

Objective Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). Material and Method We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Results Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. Conclusion TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Clinical variables associated with overall survival in metastatic castration resistant prostate cancer (mCRPC) patients treated with sipuleucel-T immunotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16565-e16565
Author(s):  
Xiao Wei ◽  
Jaselle Perry ◽  
Emily Chang ◽  
Li Zhang ◽  
Robert A. Hiatt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Performance Status ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Prior Chemotherapy ◽  
Ecog Ps ◽  
Baseline Psa

e16565 Background: Sipuleucel-T (Sip-T) is a cellular-based cancer immunotherapy for men with asymptomatic or minimally symptomatic mCRPC. Its approval was based on overall survival (OS) benefit in randomized placebo-controlled phase 3 trials. However, treatment was associated with PSA decline in only a small minority of pts. Understanding clinical factors predictive of OS may help to guide treatment decisions, including pt selection and timing of Sip-T relative to other therapies. Methods: This is a retrospective chart review of mCRPC pts treated with Sip-T at UCSF between April 2010 and April 2016. All pts completed 3 Sip-T infusions. Patients with localized prostate cancer treated with neoadjuvant Sip-T (NCT00715104) and pts with mCRPC treated with an ongoing phase 2 Sip-T/Ipilimumab trial (NCT01804465) were excluded. Kaplan-Meier method was used to estimate OS. The predictive value of candidate variables – including age, ECOG performance status (PS), Gleason score, metastatic volume, baseline PSA, baseline PSADT, prior abiraterone or enzalutamide, and prior chemotherapy – was assessed using univariate and multivariate Cox proportional hazard model. Results: Of 43 patients evaluated to date, 74.4% had ECOG PS 0, 88.4% had bone +/- nodal metastasis, 81.4% had low metastatic volume, 9.3% had prior abiraterone, 2.3% had prior enzalutamide, and 9.3% had prior chemotherapy. The median age was 69 years (range 53-85), median baseline PSA was 8.3 ng/mL (range 0.05-227.9) and median PSA doubling time (PSADT) was 3.9 mo (range 1.4-15.1). At a median follow-up of 21.4 mo, the median OS was 34.1 mo (95% CI 25.7-41.4). Univariate analysis showed that ECOG PS (HR 6.66, p < 0.001) and PSA (log-transformed) (HR 3.36, p = 0.002) were significantly associated with OS. There was a trend towards worse OS with faster baseline PSADT (log-transformed) (HR 0.16, p = 0.11) and prior chemotherapy (HR = 4.13, p = 0.11). By multivariate analysis, ECOG PS, baseline PSA and baseline PSADT were statistically significant (p < 0.05). Conclusions: In this ongoing retrospective cohort, ECOG PS, baseline PSA and baseline PSADT were associated with OS in mCRPC patients treated with Sip-T.

scholarly journals The Prognostic Role of Baseline Metabolic Tumor Burden and Systemic Inflammation Biomarkers in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223: A Proof of Concept Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3213
Author(s):  
Matteo Bauckneht ◽  
Sara Elena Rebuzzi ◽  
Alessio Signori ◽  
Maria Isabella Donegani ◽  
Veronica Murianni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systemic Inflammation ◽  
Fdg Pet ◽  
Univariate Analysis ◽  
Tumor Burden ◽  
Castration Resistant Prostate Cancer ◽  
Term Survival ◽  
Lymphocyte Ratio ◽  
Castration Resistant ◽  
Radium 223

Over the last years has emerged the urgent need for the identification of reliable prognostic biomarkers able to potentially identify metastatic castration-resistant prostate cancer (mCRPC) patients most likely to benefit from Radium-223 (Ra-223) since baseline. In the present monocentric retrospective study, we analyzed the prognostic power of systemic inflammation biomarkers and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET)-derived parameters and their potential interplay in this clinical setting. The following baseline laboratory parameters were collected in 59 mCRPC patients treated with Ra-223: neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), and systemic inflammation index (SII), while maximum Standardized Uptake Value, Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) were calculated in the 48 of them submitted to baseline FDG-PET. At the univariate analysis, NLR, dNLR, MTV, and TLG were able to predict the overall survival (OS). However, only NLR and MTV were independent predictors of OS at the multivariate analysis. Additionally, the occurrence of both increased NLR and MTV at baseline identified mCRPC patients at higher risk for lower long-term survival after treatment with Ra-223. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden and their combination might represent potentially valuable tools for identifying mCRPC patients who are most likely to benefit from Ra-223. However, further studies are needed to reproduce these findings in larger settings.

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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