Prognostic factors that affect survival outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 225-225
Author(s):  
Esmail Mutahar Al-Ezzi ◽  
Husam Alqaisi ◽  
Sarah Picardo ◽  
Marco Iafolla ◽  
Srikala S. Sridhar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bone Metastases ◽  
Cox Regression ◽  
Subsequent Treatment ◽  
Survival Outcomes ◽  
Castration Resistant Prostate Cancer ◽  
Median Baseline ◽  
Disease Characteristics ◽  
Radium 223 ◽  
Baseline Psa

225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ < 6, 6-20, > 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received > 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had > 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs > 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs > 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA < 70 ug/L (HR = 0.51; p = 0.0023), LDH < 250 U/L (HR 0.55; p = 0.0082), Hb > 120 g/L(HR 0.46; p = 0.0004), ALP < 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p < 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration > 4 cycles of Ra-223 and baseline ALP < 150 U/L were associated with improved OS. Conclusions: Men who receive > 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.

Alkaline phosphatase (ALP) normalization and overall survival in patients with bone metastases from castration-resistant prostate cancer (CRPC) treated with radium-223.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 49-49 ◽  
Author(s):  
C. Parker ◽  
C. G. O'Bryan-Tear ◽  
B. Bolstad ◽  
A. Lokna ◽  
S. Nilsson
Keyword(s):  
Overall Survival ◽  
Bone Metastases ◽  
High Energy ◽  
Serum Markers ◽  
Phase Iii ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Phase Ii Studies ◽  
Randomized Phase Ii

49 Background: Radium-223 (Alpharadin) is a first-in-class alpha-pharmaceutical. It targets bone metastases with high-energy alpha-radiation of extremely short range that spares bone marrow. Radium-223 has a profound effect on serum markers of bone metabolism, including ALP, in patients with bone metastases from CRPC. In an exploratory analysis, we studied whether this effect is associated with a meaningful clinical benefit. Methods: Patients with CRPC and bone metastases were treated in 2 randomized phase II studies. BC1-02 was a placebo-controlled study of radium-223 (50 kBq/kg) every 4 weeks for 12 weeks. BC1-04 evaluated radium-223 (25, 50, or 80 kBq/kg) every 6 weeks for 12 weeks. Baseline total ALP values > 128 U/L were considered elevated; those decreasing to below 128 U/L during treatment with radium-223 were defined as normalized, and those remaining above that value as non-normalized. Results: In BC1-02, ALP normalization was seen in 12/26 (46%) patients treated with radium-223. Median survivals of those with and without ALP normalization were 102 weeks and 42 weeks, respectively (log-rank P < 0.001). In BC1-04, ALP normalization was seen in 25/75 (33%) cases: 5/29 (17%) in the 25 kBq/kg group, 10/25 (40%) with 50 kBq/kg, and 10/21 (48%) with 80 kBq/kg, indicating a dose-response relationship. Median survivals for the 25 patients with, and the 50 patients without, ALP normalization were 102 weeks and 58 weeks, respectively (log-rank P = 0.0086). Conclusions: Inpatients with metastatic CRPC and bone metastases treated with radium-223, ALP normalization was associated with significantly better overall survival. These data support the rationale for the ongoing ALSYMPCA phase III trial of radium-223. [Table: see text]

Phase II clinical study of radium-223 chloride (BAY 88-8223) in Japanese patients with symptomatic castration-resistant prostate cancer (CRPC) with bone metastases.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 167-167
Author(s):  
Hiroji Uemura ◽  
Satoshi Nagamori ◽  
Yoshiaki Wakumoto ◽  
Hirotsugu Uemura ◽  
Go Kimura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Metastases ◽  
Phase Ii ◽  
Japanese Patients ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Phase Ii Clinical Study ◽  
Secondary Endpoints

167 Background: The ALSYMPCA study was conducted to evaluate the alpha-emitting radiopharmaceutical Radium-223 Chloride (BAY 88-8223) in patients with symptomatic bone metastases in Castration resistant prostate cancer (CRPC). This trial met its primary endpoint of overall survival at the time of pre-planned interim analysis. Post hoc analysis showed a reduction from baseline in total ALP at 12 weeks (32% reduction in the BAY 88-8223 arm vs. 37% increase in placebo arm, P < 0.001) (Sartor et al. ASCO 2013). We are reporting here a single-arm, open-label, multicenter, phase II clinical study of BAY 88-8223 in Japanese patients with symptomatic CRPC with bone metastases. Methods: Eligible patients had progressive, symptomatic CRPC with at least 2 bone metastases on bone scintigraphy and no known visceral metastases; were receiving Best Standard of Care; and either had previously received docetaxel, were docetaxel ineligible, or had refused docetaxel. Patients received 6 injections of radium-223 (50 kBq/kg IV) every 4 weeks. The primary endpoint was percentage of change in total ALP from baseline at 12 weeks. Secondary endpoints included overall survival, time to symptomatic skeletal event, percentage of change in bone ALP/PSA/biomarkers, and safety. Results: A total of 67 subjects were enrolled; 18 were screening failures, and 49 were received to the study treatment and received at least one administration from September 2013 to May 2014. The mean percent change in total ALP from baseline at 12 weeks was -19.3% (95%CI: -28.0% to -10.7%). The results of secondary endpoints will be presented. The safety and tolerability profile for BAY 88-8223 were highly favorable and only 1 subject (2.0%) experienced lymphocyte count decreased as a Grade 4 adverse event, and there was no death during the study treatment and within 30 days after the last injection of study treatment. Conclusions: The reduction from baseline in total ALP at 12 weeks seen in this phase II study is consistent with the results shown in ALSYMPCA study. Overall, BAY 88-8223 was well tolerated in Japanese patients with CRPC and bone metastases. Clinical trial information: NCT01929655.

A phase I/II study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer with bone metastases (COMRADE): A trial in progress.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS182-TPS182
Author(s):  
Justin Shaya ◽  
Wanling Xie ◽  
Biren Saraiya ◽  
Mamta Parikh ◽  
Edmund Folefac ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Metastases ◽  
Phase 1 ◽  
Parp Inhibitors ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Radium 223

TPS182 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-stranded breaks leading to cell death and has demonstrated improvement in overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. PARP inhibitors, including olaparib and rucaparib, inhibit repair of DNA single-stranded beaks and have demonstrated clinical efficacy in mCRPC patients harboring alterations in the homologous recombination repair (HRR) pathway. In extensive preclinical cancer models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the clinical hypothesis that the combination of radium-223 with olaparib will demonstrate anti-tumor activity in patients with mCRPC irrespective of underlying HRR deficiency status. Methods: This is an open label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of olaparib in combination with radium-223 in men with mCRPC with bone metastases. Patient must have 2 or more bone metastases and at least 1 bone metastasis that has not been treated with prior radiation therapy. Key exclusion criteria include the presence of visceral metastases or malignant lymphadenopathy exceeding 4 cm and prior therapy with radium-223 and/or PARP inhibitors. The phase 1 component of the study uses a 3+3 dose escalation design to determine the recommended phase 2 dose of olaparib in combination with standard of care dosing of Radium-223. The primary endpoint of the phase 1 component is safety. The phase 2 component of the study is an open-label, randomized study evaluating the combination of olaparib and radium-223 compared to radium-223 alone. The primary endpoint of the phase 2 component is radiographic progression-free survival as defined by Prostate Cancer Working Group 3 guidelines for bone metastases and RECIST v1.1 for non-bone metastases. Secondary endpoints include time to PSA progression, PSA response, time to subsequent therapy, time to first skeletal event, overall survival, and safety. Exploratory endpoints include stratification of response based on HRR alterations, whole exome sequencing of plasma cell free DNA both at baseline, on treatment, and at progression, and evaluation of changes in the tumor immune microenvironment with therapy. As of October 1, 2020, the phase 1 component has completed accrual and we anticipate opening the phase 2 component by December 2020. Clinical trial information: NCT03317392.

Clinical Characteristics, Pathology and Outcome of 237 Patients With Synovial Sarcoma: Single Center Experience

2021 ◽  
pp. 106689692110560
Author(s):  
Hao Cheng ◽  
Chi Yihebali ◽  
Hongtu Zhang ◽  
Lei Guo ◽  
Susheng Shi
Keyword(s):  
Overall Survival ◽  
Synovial Sarcoma ◽  
Tumor Size ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Tumor Diameter ◽  
Single Center ◽  
Primary Tumors ◽  
Cox Regression Analysis

Background Synovial sarcoma (SS) is a rare soft tissue sarcoma. Available data regarding survival outcomes of patients with SS still remains limited. In this study, a single center retrospective analysis was performed to investigate the clinical characteristics, pathology and survival outcomes in patients with SS in China. Methods Patient data were systematically reviewed at the National Cancer Center from January 2015 to December 2020. The general information and treatment condition of patients were collected. Overall survival (OS) was evaluated using the Kaplan-Meier and Cox regression method. Results A total of 237 consecutive patients were included in this study (follow-up cut-off date: December, 2020). The median age of patients involved was 35 years (ranging from 5 to 83 years) and the mean tumor diameter was 5.3 cm (ranging from .2 to 26.0 cm). The main findings of the immunohistochemical staining analyses were EMA (111/156) (71%), keratin (32/64) (50.0%), keratin (12/20) (60%), keratin (42/70) (60%), S-100 (18/160) (11%), BCL-2 (128/134) (96%), CD99 (137/148) (93%) and TLE1 (23/26) (88%). It was found that 109 patients (66%) were presented with monophasic subtype and 55 (34%) with biphasic subtype. A total of 137 patients were tested by FISH method and 119 patients (87%) demonstrated SS18 rearrangement, whereas 18 patients (13%) did not show SS18 rearrangement. Generally, it was found that the 3-year OS rate was 86% and the 3-year DFS was 55%. Results of univariate analysis revealed that age, tumor size, tumor site, radiotherapy and targeted therapy were significantly correlated with the overall survival ( P < .05). Further, multivariate Cox regression analysis revealed that age, tumor size and radiotherapy were significantly associated with OS ( P < .05). Conclusions In conclusion, this study shows that the outcomes of patients with SS significantly decrease with age and tumor size. It was evident that radiotherapy is an independent and positive prognostic factor for patients with SS. In addition, it was shown that the prognosis of SS varies with tumor location. For instance, primary tumors in lower extremities have a higher prognosis, whereas tumors located in thorax have a lower prognosis.

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