Real-World Outcomes of Radium-223 Dichloride for Metastatic Castration Resistant Prostate Cancer

Kuppen, Malou C.P.; Westgeest, Hans M.; Doelen, Maarten J. van der; Eertwegh, Alphonsus J. M. van den; Coenen, Jules L.L.M.; Aben, Katja K.H.; Bergh, Alphons C.M. van den; Bergman, Andries M.; Bosch, Joan van den; Dadaşer-Çelik, Filiz; Hendriks, Mathijs P.; Lavalaye, Jules; Meer, Saskia van der; Polée, Marco B.; Somford, Diederik M.; Oort, Inge M. van; Groot, Carin A. Uyl–de

doi:10.2217/fon-2020-0039

Cited by 32 publications

(21 citation statements)

References 31 publications

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“…This label change has impact on the treatment arsenal of metastatic CRPC patients. Due to the development of visceral metastases, impaired performance status and reduced hematological function in later disease stages, the window of opportunity to receive radium-223 therapy might be missed [ 4 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

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

Doelen

Stockhaus

et al. 2021

Eur J Nucl Med Mol Imaging

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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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Section: Discussionmentioning

confidence: 99%

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

Doelen

Stockhaus

et al. 2021

Eur J Nucl Med Mol Imaging

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“…Moreover, in 2018 the European Medicine Agency (EMA) restricted the use of [ 223 Ra]RaCl 2 to patients with more than six osteoblastic lesions progressing to at least two systemic therapies for mCRPC or ineligible for any systemic mCRPC treatment [ 10 ]. The consequent delay of [ 223 Ra]RaCl 2 administration in the later phases of the disease might negatively affect OS, making the patient’s selection process even further challenging [ 11 ]. In this scenario, identifying prognostic factors potentially able to select patients most likely to benefit from [ 223 Ra]RaCl 2 since baseline has become a crucial issue.…”

Section: Introductionmentioning

confidence: 99%

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

Bauckneht

Rebuzzi

Signori

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). Patients and methods Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. Results Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). Conclusions The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.

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“…These results also indicate that radium-223, as appropriate, could be considered as one of the early treatment options integrated into the management of patients with mCRPC, with no apparent adverse impact on long-term prognosis. Other real-world studies have shown correlations between overall survival and completion of 5 or 6 radium-223 injections, use of radium-223 in the first or second line, or use before chemotherapy [11][12][13][14][15][16][17][18]. Patients able to complete the full course of radium-223 injections are likely to have fewer symptoms (including less pain), less disease burden, a good performance status, low baseline PSA and ALP levels, and high baseline hemoglobin levels [11,[19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Real-world patient characteristics associated with survival of 2 years or more after radium-223 treatment for metastatic castration-resistant prostate cancer (EPIX study)

George

Agarwal

Sartor

et al. 2022

Prostate Cancer Prostatic Dis

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Background The real-world EPIX study was conducted to gather information about the characteristics of patients with metastatic castration-resistant prostate cancer (mCRPC) who survived ≥2 years after treatment with the alpha-emitter radium-223. Methods This retrospective study of electronic health records in the US Flatiron database (NCT04516161) included patients with mCRPC treated with radium-223 between January 2013 and June 2019. Median overall survival (OS) and prostate-specific antigen (PSA) response (≥50% reduction) from start of radium-223 treatment were the primary and secondary endpoints, respectively. Patient characteristics were compared between those who survived ≥2 years versus <2 years, including a subgroup who survived <6 months. Results In the 1180 patients identified, median OS was 12.9 months (95% CI: 12.1–13.7), and 13% of patients with data at 6 months had a PSA response. The survival groups included 775 patients (65.7%) who survived <2 years (including 264 (22.4%) who survived <6 months) and 185 patients (15.7%) who survived ≥2 years; 220 patients (18.6%) had incomplete follow-up data and were censored. On multivariate analysis, age >75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 2–4, visceral metastases, prior symptomatic skeletal events (SSEs), and prior chemotherapy were independently prognostic of reduced OS. For patients with survival ≥2 years versus <2 years, median age was 71 versus 75 years, 4% versus 14% had ECOG PS 2–4, 4% versus 10% had visceral metastases, 38% versus 44% had prior SSEs, and 16% versus 32% had prior chemotherapy. Conclusions In this study of men with mCRPC treated in real-world clinical practice, median OS was consistent with that seen in the phase 3 ALSYMPCA trial. Patients who survived ≥2 years after the start of radium-223 were younger and had better ECOG PS, lower disease burden, and less use of prior chemotherapy than those who survived <2 years.

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Real-World Outcomes of Radium-223 Dichloride for Metastatic Castration Resistant Prostate Cancer

Cited by 32 publications

References 31 publications

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

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

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

Real-world patient characteristics associated with survival of 2 years or more after radium-223 treatment for metastatic castration-resistant prostate cancer (EPIX study)

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