Combination radium-223 therapies in patients with bone metastases from castration-resistant prostate cancer: A review

Cursano, Maria Concetta; Iuliani, Michele; Casadei, Chiara; Stellato, Marco; Tonini, Giuseppe; Paganelli, Giovanni; Santini, Daniele; Giorgi, Ugo De

doi:10.1016/j.critrevonc.2020.102864

Cited by 20 publications

(15 citation statements)

References 49 publications

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“…Future prospective studies with power to detect OS, particularly to evaluate the effects of radium-223 plus enzalutamide, could help discern whether combination therapy is beneficial. This includes the randomized phase III EORTC-1333-GUCG/PEACE III trial (NCT02194842), which seeks to assess radiographic PFS, OS, first SSE, and time and incidence of first skeletal progression-free endpoints with radium-223 plus enzalutamide compared to enzalutamide alone in asymptomatic or mildly symptomatic patients with chemotherapy naive mCRPC [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer

et al. 2021

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Introduction Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear. Patients and methods This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms. Results A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59–2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11–3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45). Conclusion Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis.

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Section: Discussionmentioning

confidence: 99%

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer

et al. 2021

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“…A number of factors may have contributed to this increased risk including the lack of use of BHAs, the concomitant use of steroids which can increase bone fragility and depleted androgen levels associated with the combined use of ADT and abiraterone acetate, which can further increase the risk of osteoporosis. 18,24–26…”

Section: Discussionmentioning

confidence: 99%

Radium-223 in combination with enzalutamide in metastatic castration-resistant prostate cancer: a multi-centre, phase II open-label study

et al. 2021

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Background: Radium-223 and enzalutamide are approved agents for patients with metastatic castration-resistant prostate cancer (mCRPC). Combining radium-223 and enzalutamide to improve outcomes is of clinical interest due to their differing modes of action and non-overlapping toxicity profiles. Methods: This phase II study enrolled patients with mCRPC and bone metastases. Patients received six cycles of radium-223 in combination with enzalutamide, followed by enzalutamide alone. The primary endpoint was safety for the combination; secondary endpoints included radiographic/clinical progression-free survival (PFS), PSA PFS, overall survival (OS), change in alkaline phosphatase, patient-reported pain outcomes and skeletal related events. Results: Forty-five patients received the combination treatment: 42 patients (93.3%) received all six cycles. Fourteen patients (31.1%) developed grade 3 or 4 toxicities, most commonly fatigue and neutropaenia. Fractures during the combination period occurred in four patients (8.9%). A further 13 patients (28.9%) developed fractures after completing combination treatment, giving a total of 17 patients (37.8%) who developed a fracture at any time on study. The median time to fracture was greater than 17.2 months [95% confidence interval (CI), 17.2–not estimable]. The median time to PSA progression was 18.1 months (95% CI, 12.68–22.60) and the median time to radiological/clinical progression was 28.0 months (95% CI, 22.54–not reached). At the primary analysis, 19 (42.2%) out of 45 patients had died with a median OS not reached (mean 34.8 months, standard error 1.4). Conclusion: In men with progressive mCRPC and bone metastases, the combination of radium-223 and enzalutamide was tolerable with the majority of patients completing the combination treatment. Bone fractures during the combination period were uncommon; however, we did identify a higher incidence of fractures occurring in patients after completing combination treatment. Bone health agents should be administered and bone health should be closely monitored following treatment with radium-223 and enzalutamide.

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“…[201] Combinations of 223 Ra with chemotherapeutic agents (e. g., docetaxel, cabazitaxel), hormonal therapies (e. g., abiraterone, enzalutamide) to improve survival and decrease bone-related morbidity are currently being investigated. [202] However, data from a randomized, doubleblind, placebo-controlled prostate cancer trial shows an increased incidence of fractures and an increased risk of radiological non-bone progression [NCT02043678]. The European Medicines Agency has recommended restricting the use of 223 Ra to patients who have had two previous treatments for metastatic prostate or who cannot receive other treatments.…”

Section: Clinical Relevance and Outlookmentioning

confidence: 99%

Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

et al. 2021

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Nuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are based on γ-emissions of specific energies. The therapeutic technologies are based on β À -particle-, α-particle-, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease's progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost-efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.

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Combination radium-223 therapies in patients with bone metastases from castration-resistant prostate cancer: A review

Cited by 20 publications

References 49 publications

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer

Radium-223 in combination with enzalutamide in metastatic castration-resistant prostate cancer: a multi-centre, phase II open-label study

Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

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