scholarly journals Comparison of effectiveness and safety outcomes of abiraterone versus enzalutamide in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis

2020 ◽  
Vol 23 ◽  
pp. 451-461
Author(s):  
Xin Wang ◽  
Yang Hui ◽  
Shihui Wang ◽  
Xiaopeng Hu ◽  
Xiaojia Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Cognitive Impairments ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Significant Difference ◽  
Psa Response

Purpose: To compare the effectiveness and safety between abiraterone and enzalutamide in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We systematically searched for relevant articles from PubMed, Cochrane, Embase from their inception through November 4, 2019. Available articles from conferences were searched. The endpoints were prostate-specific antigen (PSA) response, overall survival (OS), progression-free survival (PFS), number of patients with any adverse event (AE). Results: 15 cohort studies involving 3546 participants were included in this meta-analysis. Pooled result showed that PSA response rate in the enzalutamide group was significantly greater than that in the abiraterone group (867 patients, risk ratio (RR) 0.69, 95% confidence interval (CI) 0.61-0.79, p＜0.00001, I2=29%). There was no significant difference in the total incidence of AEs between two groups (730 patients, RR 0.42, 95% CI 0.14-1.31, p = 0.14, I2=84%). The common adverse events observed in the published articles were fatigue and perceived cognitive impairments. Patients who received enzalutamide had the higher risk to have the feeling of fatigue compared with abiraterone group (2555 patients, RR 0.45, 95% CI 0.24-0.85, p=0.01, I2=92%). And there was no statistical difference between two groups respect to the side effect of perceived cognitive impairments (1856 patients, RR 0.94, 95% CI 0.47-1.88, p=0.85, I2=15%). Conclusions: Our results demonstrated that enzalutamide was associated with higher PSA response rate compared to abiraterone in patients with mCRPC, and no significant difference was found between two groups in the overall AE. But enzalutamide use induced higher risk of the AE of fatigue.

A study of two ODM-201 formulations with a safety and tolerability extension phase in patients with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 115-115 ◽  
Author(s):  
Christophe Massard ◽  
Teuvo L. J. Tammela ◽  
Egils Vjaters ◽  
Vilnis Lietuvietis ◽  
Petri Bono ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Capsule Formulation ◽  
Castration Resistant ◽  
Psa Response ◽  
Effect Of Food ◽  
Extension Period ◽  
Clinical Trial Information

115^ Background: This open phase I trial assessed the bioavailability, and the effect of food on the bioavailability of ODM-201 600mg tablets compared to a 600mg capsule formulation. Efficacy, safety, and tolerability of ODM-201 were studied in the extension period. Methods: The study had two parts: a pharmacokinetic (PK), and a safety and tolerability part. Dosing was 600mg bid with or without food. In the PK part, three single doses of ODM-201 were given over 3 weeks. In the extension part patients could continue treatment until disease progression or until an intolerable adverse event or condition that prevented further dosing of ODM-201. Results: Thirty men with metastatic chemotherapy-naïve castration-resistant prostate cancer (CRPC) were enrolled, the median age was 68. The median prostate-specific antigen (PSA) was 18.2 ng/mL and testosterone 23.1 ng/dL at baseline. Food interaction was observed when ODM-201 formulations were administered after a high fat content breakfast compared to administration at fast. AUC and Cmaxvalues were about 50% lower after fast. Twenty nine patients have completed the 4-week visit. The PSA response rate (50% or more PSA decline) was 86%, with a median PSA decrease of -66% (-96, 5) at week 4 (N=18/21). Most commonly reported adverse events so far are fatigue, abdominal pain, diarrhea, hematuria, and nausea. Conclusions: ODM-201 600mg bid as tablets has comparable PK to capsules used in the phase II ARADES trial. It is well tolerated and has good PSA response in chemotherapy-naïve patients with CRPC . Clinical trial information: NCT01784757.

scholarly journals Concordance between Response Assessment Using Prostate-Specific Membrane Antigen PET and Serum Prostate-Specific Antigen Levels after Systemic Treatment in Patients with Metastatic Castration Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 663
Author(s):  
Sangwon Han ◽  
Sungmin Woo ◽  
Yong-il Kim ◽  
Jae-Lyun Lee ◽  
Andreas G. Wibmer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systemic Treatment ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Response Evaluation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psma Pet ◽  
Psa Response ◽  
Specific Membrane

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

Comparing the clinical efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis

2020 ◽  
pp. 107815522092941
Author(s):  
Xin Wang ◽  
Hui Yang ◽  
Xiaopeng Hu ◽  
Wei Wang ◽  
Xiaojia Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
New Drugs ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients

Background Two new drugs, abiraterone and enzalutamide, had recently shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer. We systematically reviewed the efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer in real-world practice. Methods A search from PubMed, Web of Science, Cochrane, Embase was conducted up to 6 March 2019. Available articles from conferences were searched. The endpoint was prostate-specific antigen response, overall survival, progression-free survival, number of patients with any adverse event. Results Fourteen cohort studies involving 3469 participants were included. Pooled result showed that prostate-specific antigen response was higher for patients receiving enzalutamide than abiraterone (790 patients, odds ratio (OR) 0.47, 95% confidence interval (CI) 0.29–0.77, P = 0.003, I2=59%). Enzalutamide was significantly associated with increased adverse events rate in comparison with abiraterone (730 patients, OR 0.35, 95%CI 0.13–0.92, P = 0.03, I2=65%). There was no statistical difference between abiraterone and enzalutamide with respect to perceived cognitive impairments (1856 patients, OR 0.90, 95%CI 0.29–2.76, P = 0.85, I2=5%). Enzalutamide was significantly associated with increased fatigue risk in comparison with abiraterone (2477 patients, OR 0.46, 95%CI 0.34–0.63, P＜0.00001, I2=0%). Conclusions Our results demonstrated that enzalutamide was more efficacious than abiraterone for patients with metastatic castration-resistant prostate cancer, but was associated with a significantly elevated risk of side effects, particularly fatigue.

scholarly journals Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration

2020 ◽  
Vol 38 (32) ◽  
pp. 3763-3772 ◽  
Author(s):  
Wassim Abida ◽  
Akash Patnaik ◽  
David Campbell ◽  
Jeremy Shapiro ◽  
Alan H. Bryce ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Specific Antigen ◽  
Brca2 Gene ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Measurable Disease ◽  
Psa Response

PURPOSE BRCA1 or BRCA2 ( BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.

Prostate-specific antigen response patterns during cabazitaxel therapy in patients with metastatic castration-resistant prostate cancer

2019 ◽  
Vol 49 (11) ◽  
pp. 1043-1048 ◽  
Author(s):  
Kent Kanao ◽  
Toshiki Ito ◽  
Kiyoshi Takahara ◽  
Ryosuke Ando ◽  
Takahiro Yasui ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Prognostic Impact ◽  
Response Patterns ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Oncology Research ◽  
Number Of Patients ◽  
Psa Response

Abstract Background The objective of this study was to categorize prostate-specific antigen (PSA) response during cabazitaxel therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) into different patterns and to investigate the prognostic impact of the PSA response patterns. Methods We reviewed data from patients with mCRPC who had been treated with cabazitaxel therapy at four institutions belonging to Tokai Urologic Oncology Research Seminar. Patients eligible for this study had received at least three cycles of cabazitaxel treatment at three- or four-week intervals. The PSA response patterns were categorized as primary resistance (PR), response (RE), stabilization (ST), and fluctuating (FL). The overall survival (OS) was compared among the patterns. Results Data from a total of 50 patients were analyzed in this study. The number of patients exhibiting PR, RE, ST and FL patterns were 18 (36%), 14 (28%), 12 (24%) and 6 (12%), respectively. The median (95% CI) OS of patients with PR and RE patterns was 10.7 (5.6–15.9) and 14.9 (6.8–23.0) months, respectively, and was not reached for patients with ST and FL patterns. The OS of patients with the FL pattern was significantly better than that of patients with PR (P = 0.012) and RE (P = 0.010) patterns. Conclusion There were some patients whose PSA were fluctuating during cabazitaxel therapy in patients with mCRPC. Because the prognosis of such patients was relatively good, the judgment to discontinue the cabazitaxel therapy after PSA rise followed by decrease should be made prudently.

scholarly journals Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 10 ◽  
Author(s):  
Jiaxin Wang ◽  
Yucong Zhang ◽  
Chao Wei ◽  
Xintao Gao ◽  
Penghui Yuan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Treatment Outcomes ◽  
Prognostic Value ◽  
Response Rate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Significant Difference ◽  
Psa Response ◽  
Androgen Receptor Splice Variant

BackgroundThe prognostic value of androgen receptor splice variant 7 (AR-V7) for the treatment response of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we aimed to synthesize relevant studies that assessed the prognostic value of AR-V7 status for the treatment response of mCRPC patients treated with androgen receptor signalling inhibitors (ARSis) and chemotherapy.MethodsWe searched the PubMed, Embase, and MEDLINE databases by using the keywords AR-V7 and prostate cancer to identify relevant studies published before 25 September 2019. The main outcomes were prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS). Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale.ResultsA total of 1,545 patients from 21 studies were included. For the mCRPC patients treated with ARSis, AR-V7-positive patients had a lower PSA response rate (OR 6.01, 95% CI 2.88–12.51; P < 0.001), shorter PFS (HR 2.56, 95% CI 1.80–3.64; P < 0.001) and shorter OS (HR 4.28, 95% CI 2.92–6.27; P < 0.001) than AR-V7-negative patients. Although AR-V7-positive patients treated with chemotherapy also had a lower PSA response rate (OR 2.23, 95% CI 1.38–3.62; P = 0.001) and shorter OS than AR-V7-negative patients (HR 1.60, 95% CI 1.02–2.53; P = 0.043), there was no significant difference in PFS (HR 1.05, 95% CI 0.74–1.49; P = 0.796) between these groups. Furthermore, AR-V7-positive patients receiving ARSis had a shorter median OS than those receiving chemotherapy (HR 3.50, 95% CI 1.98–6.20; P < 0.001); There was no significant difference among AR-V7-negative patients (HR 1.30, 95% CI 0.64–2.62; P = 0.47).ConclusionsAR-V7 is a potential biomarker of treatment resistance in mCRPC patients. AR-V7-positive mCRPC patients had poorer treatment outcomes than AR-V7-nagetive patients when treated with ARSis. AR-V7-positive patients have better outcomes when treated with taxane than ARSis. Furthermore, the ability of AR-V7 status to predict treatment outcomes varies from different detection methods. The detection of AR-V7 before treatment is important for the selection of treatment modalities for mCRPC patients.

scholarly journals Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment

2021 ◽  
Vol 9 (10) ◽  
pp. e002919
Author(s):  
Sumit K Subudhi ◽  
Bilal A Siddiqui ◽  
Ana M Aparicio ◽  
Shalini S Yadav ◽  
Sreyashi Basu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Measurable Disease

BackgroundImmune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone.HypothesisCombined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone.Patients and methodsIn this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline.ResultsTwenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints.ConclusionsTremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment.Trial registration numberNCT03204812.

Abiraterone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and MDV3100.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
Ecaterina Ileana ◽  
Yohann Loriot ◽  
Laurence Albiges ◽  
Christophe Massard ◽  
Aurore Blesius ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Patient Characteristics ◽  
Preliminary Evidence ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Symptom Response ◽  
Psa Response ◽  
Metastatic Sites

4554 Background: Chemotherapy with docetaxel is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). In patients progressing after docetaxel, both abiraterone and MDV3100 have yielded improved survival for patients with mCRPC. The efficacy of abiraterone in patients pre-treated with MDV 3100 is unknown. Methods: We investigated abiraterone-prednisone in 24 patients with cancer progression after docetaxel followed by MDV3100. All patients received abiraterone 1000 mg/day plus prednisone 10mg/day. Prostate-specific antigen (PSA) response, symptom response, and time to progression were assessed. Results: Patient characteristics were as follows: median age: 74 years (53-84), median PSA: 108 ng/mL (2-2541), metastatic sites: bone: all 24 patients, liver/lung: 6 patients (25%), and lymph nodes : 9 patients (38%). Five patients (21%) had a PSA decrease on abiraterone-prednisone. Three patients (13%) achieved a PSA response, defined as a decrease of >50% in PSA, confirmed after≥ 4 weeks. The duration of PSA response was 2, 3 and 4.5 months. Six patients (29%) had a symptomatic response on the pain score and analgesic consumption was decreased. Treatment was well tolerated. Abiraterone-prednisone was discontinued in one patient due to edema and hypokaliemia. Conclusions: This study shows preliminary evidence that abiraterone-prednisone yields activity in patients with mCRPC pretreated with docetaxel and MDV3100.

The effect of prior abiraterone (Abi) use on the activity of enzalutamide (Enza) in men with mCRPC.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 18-18 ◽  
Author(s):  
Heather H. Cheng ◽  
Rosa Nadal ◽  
Roman Gulati ◽  
Arun Azad ◽  
Przemyslaw Twardowski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Subsequent Treatment ◽  
Significant Response ◽  
Castration Resistant Prostate Cancer ◽  
Steroid Use ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
Psa Response ◽  
Time Of Presentation

18 Background: Enzalutamide (Enza) and abiraterone (Abi) are next generation hormonal agents for metastatic castration resistant prostate cancer (mCRPC). Whether these agents can be effectively sequenced is not yet well understood. Results of retrospective analyses of Abi after prior Enza have demonstrated modest responses of brief duration, suggesting common resistance pathways. Here, we retrospectively analyze response to Enza with or without prior Abi treatment. Methods: We retrospectively reviewed 195 patients from seven academic centers treated with Enza between January 2009 and August 2013. Data were collected on disease characteristics, prior therapies, and prostate-specific antigen (PSA) values at baseline and while on treatment. Logistic regression was used to evaluate association between 30% or greater PSA decline on Enza and either prior Abi treatment or 30% or greater PSA decline on prior Abi after accounting for potential confounders. Results: One hudred eighty three patients had non-missing PSA starting and nadir values on Enza, with starting PSA median 102.0 (range 1.1–5007.0) ng/mL. Overall, 42% (76 of 183) of Enza-treated patients achieved a 30% or greater PSA decline, with 39% (58 of 150) response among prior Abi-treated patients and 55% (18 of 33) response among Abi-naïve patients. Of 79 patients who lacked significant response to prior Abi, 30% (25 of 79) achieved a 30% or greater PSA decline and 19% (15 of 79) achieved a 50% or greater PSA decline with subsequent Enza. Odds of achieving a 30% or greater PSA response on Enza was 2.3 times higher for Abi-naïve patients versus prior Abi-treated patients (95% CI 1.0–5.5, P=0.06) and 1.9 times higher for Abi-responders vs Abi-non-responders (95% CI 1.0–3.7, P=0.06) after adjusting for prior docetaxel and concurrent steroid use. Conclusions: In this multi-center retrospective study, 39% of patients achieved a 30% or greater PSA decline with Enza after prior Abi treatment. While the activity of Enza appears to be blunted in the post-Abi setting, PSA declines still occur in a meaningful proportion of patients. Notably, 30% of patients without significant response to prior Abi responded to subsequent treatment with Enza, suggesting a subset of men with distinct biological resistance pathways. Data will be updated at the time of presentation.

A meta-analysis on individual data of bone-targeting radio-isotopes in men with bone metastases from castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 352-352
Author(s):  
Safae Aarab Terrisse ◽  
Chris C. Parker ◽  
Karamouza Eleni ◽  
A. Oliver Sartor ◽  
Nicholas James ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Meta Analysis ◽  
External Beam Radiotherapy ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Significant Difference ◽  
Radio Isotopes

352 Background: Among bone-targeted radio-isotopes (RI), Radium-223 (an α-emitter) is the only one with clearly demonstrated overall survival (OS) benefit in men with castration-resistant prostate cancer (CRPC). The aim of this meta-analysis is to estimate the OS impact of RI in men with CRPC. Methods: An individual patient data meta-analysis was carried out from randomized trials with inclusion period 1993-2013. Eligible trials included more than 50 patients, mandated bone metastases from CRPC and randomly evaluated RI. Endpoints were OS (primary), symptomatic skeletal events (SSE) and toxicity. A fixed-effect model was used. The log-rank test stratified by trial was used to estimate individual and overall hazard ratios (HR). Subset analyses were performed by the type of radiation (α vs. β emission) and by trial comparison: RI + Chemotherapy (CT) vs. CT, RI+ External beam radiotherapy (EBRT) vs. EBRT, RI vs. EBRT. Results: From 9 identified trials, data from 6 trials comprising 2081 patients (min: 64, max: 921) were collected with 2 trials representing 80% of data. The data from 3 trials (n = 341) were not available. The overall effect on OS favoured RI with HR = 0.86 [0.77-0.95] but high heterogeneity between trials (p < 0.001, I2= 79.6%). The overall effect of α- emitters on OS (HR = 0.70 [0.58; 0.83], 2 trials, n = 985) significantly differed from that of β-emitters (HR = 0.96 [0.84; 1.10], n = 4 trials, n = 1096) (interaction p = 0.0041). The overall effect on SSE favoured RI with HR = 0.81 [0.69-0.93] (4 trials, n = 1806) with marked between trial heterogeneity (p = 0.08, I² = 55.3%) and a significant difference (p = 0.02) by the type of RI (α-emitters: HR = 0.65 [0.52-0.82]-2 trials, β-emitters: HR = 0.93 [0.77-1.13]-2 trials). Conclusions: In men with metastatic CRPC a significant improvement of OS and SSE was obtained with bone targeted α-emitter radio isotopes, but not with β-emitter. However, some between trial heterogeneity of effects on OS need further investigations.

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