Contemporary use of radium-223 (Ra-223) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC): Feasibility and safety.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 210-210 ◽  
Author(s):  
Hamid Emamekhoo ◽  
Rajasree Pia Chowdry ◽  
Paul Elson ◽  
Elisa M. Ledet ◽  
Allison Martin ◽  
...  
Keyword(s):  
Bone Matrix ◽  
Cleveland Clinic ◽  
Safety Data ◽  
Median Number ◽  
Abiraterone Acetate ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Psa Progression ◽  
Pre Treatment

210 Background: Ra-223 is an α-emitter that binds to the newly formed bone matrix and targets osteoblastic metastatic lesions. Treatment with Ra-223 delays symptomatic skeletal-related events (SREs) and improves overall survival (OS) in men with mCRPC. Concerns about the efficacy and safety of Ra-223 in the pre-chemotherapy space, given alone or in combination with Abiraterone Acetate (AA) or enzalutamide (ENZ), have been raised. Methods: To determine the feasibility, efficacy and safety profile of Ra-223 given alone or in combination with AA or ENZ to men with docetaxel-naïve mCRPC a retrospective study was conducted. PSA decline, rPFS and safety data for patients (pts) treated at Cleveland Clinic (CC) and Tulane University (TU) were analyzed. Results: Fifty-one (27 CC and 24 TU) chemo-naïve mCRPC pts with bone metastases were identified. The median age was 63 (46-87). Testosterone suppression was maintained during treatment. Pre-treatment alkaline phosphatase (ALP) was elevated in 16 pts (33%). In addition to bone, 24 pts (47%) had soft-tissue metastases. While 23 pts received Ra-223 alone, 22 pts (43%) received concomitant AA or ENZ therapy. To date, the median number of Ra-223 cycles received is 5 (1-6) with 39% of pts (20/51) receiving all 6 cycles. PSA declines >30% were observed in 31% of pts. All but one pt had at least some decline in ALP. ALP decline >30% was observed in 68% of pts. Reasons for treatment discontinuation included; completion of 6 cycles 39% (20/51); PD 35% (18/51); AEs 8% (4/51) and pt choice 4% (2/51). Grade (G) 3/4 AEs were observed in 4 pts; G3 anemia (n=3) and G4 thrombocytopenia (n=1). The vast majority of pts had PSA progression (81%) and 42% of pts have died. Estimated median time to PSA progression and OS are 3.9 (95% C.I. 1.84-4.82) and 11.0 months (95% C.I. 7.5-16.4), respectively. Pts with normal baseline hemoglobin levels and those who received concomitant AA tended to have better PSA progression-free and OS (p<.06). Conclusions: Treatment with Ra-223 in combination with AA or ENZ in chemo-naïve mCRPC pts is feasible with no new safety signals of concern. Further evaluation of the combination of AA or ENZ with Ra-223 in this setting is warranted.

Treatment patterns for metastatic hormone-sensitive prostate cancer (mHSPC) progressing after up-front docetaxel in combination with androgen deprivation therapy (D-ADT).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 305-305
Author(s):  
Pedro C. Barata ◽  
Hamid Emamekhoo ◽  
Prateek Mendiratta ◽  
Dharmesh Gopalakrishnan ◽  
Vadim S. Koshkin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Response ◽  
Cleveland Clinic ◽  
Final Analysis ◽  
High Volume ◽  
Median Number ◽  
Subsequent Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Visceral Disease

305 Background: D-ADT increases overall survival (OS) in men with mHSPC. All patients (pts) however progress and develop castration-resistant prostate cancer (CRPC). Little is known about response to subsequent therapy and outcomes in this setting. Methods: Retrospective analysis of consecutive mHSPC pts treated with ≥3 cycles of D-ADT at Cleveland Clinic and University of Wisconsin-Madison. We aimed to describe baseline, progression characteristics, treatment choices, sequence and outcome of subsequent therapy. Results: A total of 146 mHSPC pts were treated with D-ADT (6% 1-2 cycles; 94% ≥3 cycles). Final analysis included 136 pts, median age 65 (range 35-86), 65% GS≥8, 79% high-volume disease. Median number of D cycles was 6 (1-6). PSA declined to “0” at 12 and 24 months in 32% and 25% of pts, respectively. Median time to CRPC (biochemical, clinical or radiographic) was 19.6 months (95% CI, 16.6-22.6). 57 pts (42%) received ≥1 subsequent treatment after CRPC [46 hormonal therapy (HT) (21 abiraterone acetate, 19 enzalutamide, 6 ASN-001); 4 Sipuleucel-T; 4 radium-223, 5 chemotherapy (2 carboplatin-based, 2 cabazitaxel, 1 D); 3 temsirolimus/bevacizumab]. Treatment response was independent from time to CRPC (≥12 months, p = 0.264). Pts receiving HT as the first subsequent treatment had a median rPFS of 13.3 months (95% CI, 10.1-16.5) compared with 3.1 months (95% CI, 0-15.8) for non-HT (p = 0.332). Treatment choice was independent of GS (p = 0.513), visceral disease (p = 0.374) and time to CRPC (p = 0.500). Most CRPC pts treated with ≥2 lines of therapy received one HT (n = 21) followed by a different HT (43%), chemo (38%), radium-223 (14%) or olaparib (10%). 57% of pts were alive at 2 years. Longer OS correlated with time to CRPC (p = 0.010) and first subsequent treatment with HT (p = 0.009) but not with visceral disease (p = 0.258), GS (p = 0.599) or sequence of therapies received (HT/HT vs HT/non-HT, p = 0.836). Conclusions: Prior D-ADT did not preclude subsequent treatment response in CRPC pts, independent of time to CRPC. The choice of first-line treatment for CRPC may impact survival in favor of those who start HT.

Randomized phase II trial of radium-223 (RA) plus enzalutamide (EZ) versus EZ alone in metastatic castration-refractory prostate cancer (mCRPC): Final efficacy and safety results.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 135-135
Author(s):  
Adam Kessel ◽  
Taylor Ryan McFarland ◽  
Nicolas Sayegh ◽  
Kathryn Morton ◽  
Deepika Sirohi ◽  
...  
Keyword(s):  
Standard Dose ◽  
Statistical Significance ◽  
Safety Data ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Clinical Cancer Research ◽  
Radium 223 ◽  
Psa Progression

135 Background: We previously reported that treatment with EZ+RA was associated with a decline in serum bone metabolism markers (BMM), which correlated with improved outcomes compared to EZ alone (Agarwal N et al, Clinical Cancer Research, 2020, PMID 31937614). Here we report the final efficacy and safety results for this trial. Methods: In this phase 2 trial (NCT02199197), patients (pts) with progressive mCRPC were treated with EZ (160 mg daily) ±RA (standard dose of 55 kBq/kg IV Q4 weeks x 6), until disease progression or unacceptable toxicities. Primary objectives of change in bone markers and safety have been reported previously. Secondary objectives included comparison of PSA progression free survival (PFS), overall survival (OS), and long term safety in all pts receiving RA+EZ vs EZ alone. Post hoc analysis included comparison of PSA-PFS2 (defined as time from start of protocol therapy to PSA progression on subsequent therapy or death whichever occurred earlier), time to subsequent/next therapy (TTNT), and long term safety. Survival analysis and log-rank tests was performed using the R statistical package v.4.0.2 ( https://www.r-project.org ). Statistical significance was defined as P<0.05. Results: Between 08/2014 and 11/2017, 47 pts were eligible and enrolled. Median follow up was 22 months (range 3.2-71.5). Thirty-five pts received RA+EZ and 12 pts received EZ alone. Receipt of prior abiraterone was allowed and was balanced between two groups: 60% in RA+EZ vs. 64% in EZ pts. Final efficacy results: TTNT, PSA-PFS2 were significantly improved in the RA+EZ pts over EZ alone pts, and all other efficacy parameters were numerically improved in RA+EZ pts (Table). Final safety results: none of the 12 EZ alone pts had any fracture; two of 35 RA+EZ pts were found to have incidental grade 1 asymptomatic fracture at the site of bone metastasis on routine imaging, at 15 and 31 months respectively after the last dose of RA, and did not require any intervention. No patients developed bone marrow disorders during the follow-up period. Efficacy and safety data will be elaborated during the meeting. Conclusions: In our study, EZ+RA resulted in significant long-term clinical benefit over EZ alone in pts with mCRPC without compromising safety. * NA&BLM; equal contribution. Clinical trial information: NCT02199197. [Table: see text]

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

scholarly journals Radium-223 in metastatic castration-resistant prostate cancer (mCRPC): efficacy and safety in real-life experience

2017 ◽  
Vol 28 ◽  
pp. vi23-vi24
Author(s):  
S.E. Rebuzzi ◽  
A. Prelaj ◽  
C. Pozzi ◽  
C. Ferrara ◽  
V. Frantellizzi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Life Experience ◽  
Real Life ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223

Novel therapies and emerging strategies for the treatment of patients with castration-resistant prostate cancer

2017 ◽  
Author(s):  
Deborah Mukherji ◽  
Aurelius Omlin ◽  
Carmel Pezaro ◽  
Johann De Bono
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
New Treatments ◽  
Phase Iii Studies ◽  
Clinical And Translational Research

Castration-resistant prostate cancer (CRPC) represents a final stage of this malignancy for many men and is defined as the progression of prostate cancer despite castrate levels of testosterone. CRPC may present as a rising PSA, the development of new metastases, or worsening of known metastases. Recent advances have resulted in five new treatments for CRPC: the immunotherapy sipuleucel-T; the cytotoxic cabazitaxel; the androgen biosynthesis inhibitor abiraterone acetate; the radioisotope radium-223; and the antiandrogen enzalutamide. These have all improved overall survival in randomized phase III studies for patients with metastatic CRPC. Furthermore, multiple agents and combinations are currently in late-stage clinical testing. Men with advanced prostate cancer represent an important population for clinical and translational research and clinical trial participation should be considered as part of standard care.

Recent Developments in Treatments for Metastatic Castration-resistant Prostate Cancer—A Mechanistic Perspective

2012 ◽  
Vol 08 (02) ◽  
pp. 89
Author(s):  
Guru Sonpavde ◽  
E David Crawford ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Microtubule Inhibitor ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Radium 223

Over the past decade, the treatment landscape in metastatic castration-resistant prostate cancer (CRPC) has markedly changed, with the introduction of three new chemotherapeutic agents. The mechanism of CRPC is not fully understood, but it may result from multiple pathways, including a loss or androgen receptor (AR) specificity and increased downstream signalling activity that provide multiple targets for therapeutic agents. For some years, docetaxel was the mainstay of treatment in CRPC, but recently, cabazitaxel (a microtubule inhibitor), sipuleucel-T (a cancer vaccine), and abiraterone acetate (a CYP17 inhibitor) were approved for CRPC treatment. In Phase III clinical trials, these agents have shown significant improvements in survival—over mitoxantrone (for cabazitaxel) and over placebo (for sipuleucel-T and abiraterone acetate)—and were well tolerated. There are also two treatments in late-stage development, MDV3100 (an oral AR antagonist) and radium-223 (an isotope that creates breaks in double-stranded DNA). These have also shown improvements in survival in Phase III trials; their regulatory approval is expected soon. The modes of actions of the existing and new drugs in CRPC are varied, but some are complementary and investigations of different combinations of these medications are much needed; they may enhance efficacy, further extend survival, and improve outcomes in this formerly untreatable disease.

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