Prostate Cancer Foundation 2018 Scientific Retreat

Prostate Cancer Foundation 2018 Scientific Retreat

The Prostate Cancer Foundation: A Discussion with Andrea Miyahira


Prostate Cancer Foundation 2018 Scientific Retreat

Prostate Cancer Foundation 2018 Scientific Retreat

The Process of Metastasis in Prostate Cancer


European Society for Medical Oncology 2018 Congress

European Society for Medical Oncology 2018 Congress

A Renewed Analysis of ERA 223


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VAIL, CO USA ( - Background: Radium-223 is a targeted alpha-emitter that selectively binds to bone metastases with high-energy, short-range (< 100 μm) alpha-particles, and is approved by the US Food and Drug Administration and European Commission for treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease.

In ALSYMPCA, radium-223 significantly prolonged overall survival compared with placebo and had a highly favorable safety profile. The incidence of grade 3 and 4 hematologic adverse events (AEs) was low: anemia in 13% and 13%; neutropenia in 2% and 1%, and thrombocytopenia in 6% and 2% of radium-223 and placebo groups, respectively. Here we report a post hoc analysis of hematologic AEs based on ALSYMPCA baseline prognostic factors. Since the incidence of grade 3 and 4 events was low, this analysis included grade 2-4 hematologic AEs.

24th cap updateMethods: Patients with progressive, symptomatic CRPC with ≥ 2 bone metastases were randomized 2:1 to radium-223 (50 kBq/kg IV) q 4 wk (n = 600) or matching placebo (n = 301). The relationships of hematologic toxicity and 6 baseline factors (study treatment, current bisphosphonate use, prior docetaxel use, extent of disease > 6 metastases including superscan, prior external beam radiation therapy [EBRT] for bone pain, and total alkaline phosphatase [ALP]) were assessed at baseline, week 24, and follow-up (40 wk after first study drug dose) using multivariate Cox regression analysis.

Results: In the regression analysis of grade 2-4 hematologic AEs, prior docetaxel (vs no prior docetaxel) was associated with a greater risk for anemia (HR = 1.41, P = 0.01), neutropenia (HR = 2.73, P = 0.03), and thrombocytopenia (HR = 2.47, P < 0.01). Treatment with radium-223 was associated with a greater risk of neutropenia (HR = 3.95, P = 0.02) and thrombocytopenia (HR = 2.14, P = 0.01). Higher baseline ALP (≥ 220 U/L) and greater extent of disease (≥ 6 metastases/superscan) were more strongly associated with an increased risk of anemia (HR = 2.78, P < 0.0001; HR = 4.35, P < 0.0001) than of thrombocytopenia (HR = 1.74, P = 0.02; HR = 3.58, P = 0.03). No differences were seen in risk of hematologic AEs with bisphosphonate use or prior EBRT for bone pain. Blood transfusions were required for 137/614 (22%) and 69/307 (22%) of radium-223 and placebo patients, respectively. Sepsis occurred in 7/600 (1%) of radium-223 patients and 6/301 (2%) of placebo patients.

Conclusions: Prior docetaxel, radium-223 treatment, higher baseline ALP, and greater extent of disease were predictors of grade 2-4 hematologic AEs. The risk for anemia (HR = 4.35) or thrombocytopenia (HR = 3.58) increased with greater extent of disease, and the risk for neutropenia increased with radium-223 treatment (HR = 3.95). These results reflect the advanced nature of CRPC among ALSYMPCA patients. Therefore, a large proportion of observed hematologic AEs may be an expected consequence of disease progression rather than study drug treatment.

Presented by Joe M. O’Sullivan, Dimitris Voliotis, Dag Clement Johannessen, Anders Widmark, Isabel Syndikus, Nicholas James, Marcos Dall’Oglio, Ingvild Haugen, Andrew Cross, Jose Garcia- Vargas, and Nicholas Vogelzang at the 24th International Prostate Cancer Update - February 19 - 22, 2014 - Cascade Conference Center - Vail, Colorado USA

Centre for Cancer Research and Cell Biology, Queen’s University, Belfast, Northern Ireland;
Bayer HealthCare, Whippany, NJ, USA;
Ullevål University Hospital, Oslo, Norway;
Umeå University,Umeå, Sweden;
Clatterbridge Center for Oncology, Wirral, UK;
Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, Birmingham, UK;
Hospital das Clínicas, Faculdade de Medicina da USP, Instituto do Câncer do Estado de São Paulo, Brazil;
Algeta ASA, Oslo, Norway;
Sheffield Hallam University, Sheffield, UK;
Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA

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