One-Year Postapproval Clinical Experience with Radium-223 Dichloride in Patients with Metastatic Castrate-Resistant Prostate Cancer

223 Background: Radium 223 (Ra-223) is a FDA and EMA approved alpha particle radiopharmaceutical used to treat men with metastatic castrate resistant prostate cancer (mCRPC) with symptomatic bone metastasis. In view of emerging systemic options, new EMA 2018 licence indication is for 3rd line onwards. We aim to evaluate the impact of systemic therapy sequencing on survival outcomes from a heterogeneous cohort of 228 patients treated with Ra-223 in a single UK centre. Methods: We prospectively collected data from 228 men underwent Ra-223 therapy for mCRPC between April 2014 and August 2018. Survival outcomes in relation to sequence of systemic treatment used prior to Ra-223 were analysed. Results: Medium age = 72 (51-87) years. Most patients (n = 142, 69%) received at least one systemic agent prior to Ra-223: docetaxel and/or cabaxitaxel chemotherapy (n = 60, 29%), abiraterone (n = 62, 30.1%) and enzalutamide (n = 67, 32.5%) in various sequences. No patients received concurrent Ra-223 /systemic treatment other than LHRH analogue. Key findings are summarized in table below. Conclusions: Our data demonstrated better survival trend in patients who received Ra-223 early. Patients who received prior chemotherapy have worse survival compared with those who were chemo-naïve likely due to bone marrow depletion. Ra-223 should not be offered to patients who have already had both cabaxitaxel and docetaxel as their medium survival is too poor to justify a treatment which takes 6 months to complete.[Table: see text]

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Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.228 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 228-228

Author(s):

Niamh Peters ◽

John Gaffney ◽

Emma Connolly ◽

Richard Bambury ◽

Derek Gerard Power ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Alkaline Phosphatase ◽

Real World ◽

Median Number ◽

Prior Chemotherapy ◽

Factors Associated ◽

Radium 223 ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.

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Exploring the effects of abiraterone/enzalutamide failure prior to the initiation of radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.214 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 214-214 ◽

Cited By ~ 2

Author(s):

Patrick Cotogno ◽

Elisa M. Ledet ◽

Allie E. Steinberger ◽

Rajasree Pia Chowdry ◽

Michael Stolten ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Strong Association ◽

Optimal Timing ◽

Data Sets ◽

Prognostic Variables ◽

Kaplan Meier ◽

Radium 223 ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

214 Background: FDA approval of three life-prolonging agents for metastatic castrate resistant prostate cancer (mCRPC) has occurred since April 2011. Two agents, abiraterone (abi) and enzalutamide (enza), disrupt androgen signaling. The third, radium-223 dichloride (Ra-223), targets bone metastases via alpha radiation. We sought to explore associations between prior abi/enza progression, number of Ra-223 cycles, prognostic factors, and overall survival (OS). Methods: Forty-two mCRPC patients (pts) treated with Ra-223 were identified. The sample was stratified based on progression (or not) on abi or enza prior to starting Ra-223. Number of Ra-223 doses administered, prognostic variables before Ra-223 treatment, and Kaplan-Meier estimates of overall survival (OS) were compared. Results: A strong association (p = 0.016) was demonstrated between prior abi/enza failure and number of Ra-223 doses administered. Patients without prior abi/enza failure were more likely to receive ≥ 4 doses of Ra-223 (94.12% vs 60.0%; odds ratio [OR] = 10.667; 95% CI, 1.214 – 93.699; p = 0.033). In comparison, those not receiving at least 4 doses of Ra-223 had a negative predictor in OS (p = .001) with a median survival of 89 days (n = 10; 95% CI, 44.064 – 133.936) compared to 303 days (n=15; 95% CI, 170.452 – 435.548). Patients initiating Ra-223 treatment after abi/enza progression had a higher median PSA (207.5 vs 49.2 ng/mL, p = 0.001), LDH (315 vs 253.5 U/L, p = 0.007) and alkaline phosphatase (ALP) (191 vs 106 U/L, p = 0.004). Conclusions: Our retrospective single institution analysis indicates that mCPRC patients who previously failed abi/enza are significantly less likely to complete 4 or more Ra-223 doses. These patients had significantly worse prostate cancer by a variety of standard prognostic variables. More information is needed from larger data sets to better understand this patient population and to best determine the optimal timing of Ra-223 administration.

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Circulating tumor cells as a predictive marker for response in patients with metastatic castrate resistant prostate cancer treated with Radium 223

European Urology Supplements ◽

10.1016/s1569-9056(16)30458-4 ◽

2016 ◽

Vol 15 (13) ◽

pp. e1675-e1676 ◽

Cited By ~ 1

Author(s):

F. Racca ◽

D. Castellano ◽

C. Suárez ◽

Arija J.A. Arranz ◽

Vidal M.J. Méndez ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Predictive Marker ◽

Radium 223 ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

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Disparity in public funding of therapies for metastatic castrate-resistant prostate cancer across Canadian provinces

Canadian Urological Association Journal ◽

10.5489/cuaj.5378 ◽

2018 ◽

Vol 12 (10) ◽

Cited By ~ 1

Author(s):

Dixon T.S. Woon ◽

Thenappan Chandrasekar ◽

Lorne Aaron ◽

Naveen S. Basappa ◽

Kim N. Chi ◽

...

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Prince Edward Island ◽

Public Funding ◽

Abiraterone Acetate ◽

Radium 223 ◽

Castrate Resistant Prostate Cancer ◽

Canadian Provinces ◽

Castrate Resistant

Introduction: Treatment using abiraterone acetate plus prednisone, enzalutamide, cabazitaxel, and radium-223 (Ra-223) improves overall survival (OS) and quality of life for patients with metastatic castrate-resistant prostate cancer (mCRPC). Despite their proven benefits, access to these therapies is not equal across Canada.Methods: We describe provincial differences in access to approved mCRPC therapies. Data sources include the pan-Canadian Oncology Drug Review database, provincial cancer care resources, and correspondence with pharmaceutical companies.Results: Both androgen receptor-axis-targeted therapies (ARATs), abiraterone acetate plus prednisone and enzalutamide, are funded by provinces in the pre-and post-chemotherapy setting, however, sequential ARAT use is not funded. “Sandwich” therapy, where one ARAT is used pre-chemotherapy and a second is used upon progression on chemotherapy, is funded in six provinces: Ontario (ON), Alberta, New Brunswick, Prince Edward Island (PEI), Nova Scotia (NS), and Newfoundland and Labrador. Ra-223 is funded in five provinces: ON, Quebec (QC), British Columbia (BC), Saskatchewan, and Manitoba to varying degrees; ON allows Ra-223 either pre- or post-chemo (not both); QC allows Ra-223 post-chemo unless chemo is not tolerated; BC allows Ra-223 if other life-prolonging mCRPC therapies have been received or ineligible. Cabazitaxel is funded in all provinces post-docetaxel, except QC and PEI. Cabazitaxel is not funded as fist-line treatment for mCPRC or in combination with other agents. In ON, BC, QC, and PEI, cabazitaxel is not funded after progression on an ARAT in the post-chemotherapy setting.Conclusions: While all provinces have access to docetaxel and ARATs, sandwiching sequential ARATs with docetaxel is funded only in select provinces. Ra-223 and cabazitaxel access is not ubiquitous across Canada. Such inequalities in access to life-prolonging therapies could lead to disparities in survival and quality of life among patients with mCRPC. Further research should quantify interprovincial variation in outcomes and cost that may result from variable access.

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