scholarly journals A novel prediction model for the completion of six cycles of radium-223 treatment and survival in patients with metastatic castration-resistant prostate cancer

2021 ◽  
Author(s):  
Yasuhide Miyoshi ◽  
Sohgo Tsutsumi ◽  
Masato Yasui ◽  
Takashi Kawahara ◽  
Ko-ichi Uemura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prediction Model ◽  
Predictive Factors ◽  
Treatment Completion ◽  
Castration Resistant Prostate Cancer ◽  
Entire Cohort ◽  
Castration Resistant ◽  
Radium 223 ◽  
Group 3 ◽  
Group 2

Abstract Purpose We evaluated the predictive factors for completion of all six cycles of radium-223 (Ra-223) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). We also developed a novel prediction model for Ra-223 treatment completion using these predictors. Methods We retrospectively reviewed data from 122 patients with mCRPC who were treated with Ra-223. The predictive factors for the completion of six cycles of Ra-223 treatment were evaluated. Statistically significant predictive factors were then used to develop a prediction model for treatment completion. Finally, using this prediction model, we classified the overall survival (OS) of the entire cohort into three groups. Results We identified three significant variables as the predictive factors for treatment completion: baseline alkaline phosphatase (ALP) level, baseline hemoglobin (Hb) level, and baseline pain. The three groups generated using the prediction model were: group 1 (patients with three predictive factors, i.e., ALP < median, Hb ≥ median, and no pain), group 2 (patients with one to two predictive factors), and group 3 (patients without any predictive factors). The treatment completion rates differed between the three groups significantly. Furthermore, the OS also differed among the groups significantly. Conclusion Our study suggested that the baseline ALP level, baseline Hb level, and baseline pain were the predictive factors of completion of all six cycles of Ra-223 treatment in patients with mCRPC. Our prediction model consisting of these factors could predict not only the completion of Ra-223 treatment, but also the post-treatment survival. This model can thus be useful for selection of patients for Ra-223 treatment.

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.

scholarly journals Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer

2020 ◽  
Vol 16 (19) ◽  
pp. 1371-1384 ◽  
Author(s):  
Malou CP Kuppen ◽  
Hans M Westgeest ◽  
Maarten J van der Doelen ◽  
Alphonsus JM van den Eertwegh ◽  
Jules LLM Coenen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
The Netherlands ◽  
Real World ◽  
Treatment Completion ◽  
Window Of Opportunity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Skeletal Event

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line ≥3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line ≥3 (HR: 3.267; 95% CI: 1.689–6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014–2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events.

Value of bone scan index for predicting overall survival among patients treated with radium-223 for bone metastatic castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Shuko Yoneyama ◽  
Yasuhide Miyoshi ◽  
Sohgo Tsutsumi ◽  
Takashi Kawahara ◽  
Yusuke Hattori ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Bone Scan ◽  
Continuous Variables ◽  
Castration Resistant Prostate Cancer ◽  
Bone Scan Index ◽  
Entire Cohort ◽  
Castration Resistant ◽  
Radium 223

216 Background: The objective of this study was to evaluate the bone scan index (BSI) as a prognostic biomarker for overall survival (OS) among patients treated with radium-223 (Ra-223) for bone metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 42 men who had been treated with Ra-223 for bone metastatic CRPC between 2012 and 2017 and investigated correlations between the baseline clinical factors of age, time to CRPC, previous use of docetaxel, PSA, Gleason score, alkaline phosphatase (ALP), and BSI and OS by multivariate analysis using the Cox proportional hazard model. We also analyzed the correlations between OS and absolute BSI value or BSI change from baseline after 12 weeks of treatment. Continuous variables were classified as dichotomous. Results: The median age, PSA, and time to CRPC were 75.5 years, 42.8 ng/mL, and 11.2 months, respectively. The median observation period was 11.7 months. Twenty-five (59.5 %) of the 42 patients had completed six cycles of Ra-223 treatment. Twenty-two patients (52.4 %) had died, including 20 (47.6 %) of cancer, by the time of analysis. The median OS in the entire cohort was 20.7 months. Multivariate analysis also showed that only BSI (≥1.5 vs. < 1.5, HR 3.72, 95% CI 1.17–11.79, p = 0.026) was significantly correlated with OS. The BSI had decreased in 16 (51.6%) of the 31 patients who had undergone bone scans after 12 weeks of treatment . Multivariate analysis showed that absolute BSI value after 12 weeks treatment was significantly correlated with OS (BSI (≥2.0 vs. < 2.0%, HR 13.07, 95% CI 2.61–65.53, p = 0.002). No correlation was found between BSI change from baseline after 12 weeks and OS. Conclusions: According to multivariate analysis, both baseline BSI and PSA were significant prognostic factors for OS among men treated with Ra-223. Absolute BSI value after 12 weeks of Ra-223 treatment was also found to be an independent prognostic factor for OS.

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.

Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Silke Gillessen ◽  
Ananya Choudhury ◽  
Alejo Rodriguez-Vida ◽  
Franco Nole ◽  
Enrique Gallardo Diaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Analysis ◽  
Phase Iii ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Continuous Administration ◽  
Castration Resistant ◽  
Radium 223 ◽  
Safety Population

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document