scholarly journals The Prognostic Value of Androgen Receptor Splice Variant 7 in Castration-Resistant Prostate Cancer Treated With Novel Hormonal Therapy or Chemotherapy: A Systematic Review and Meta-analysis

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhize Wang ◽  
Haixiang Shen ◽  
Nieying Ma ◽  
Qinchen Li ◽  
Yeqing Mao ◽  
...  
Keyword(s):  
Hormonal Therapy ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Positive Proportion ◽  
Castration Resistant ◽  
Hazard Ratios ◽  
Psa Response ◽  
Androgen Receptor Splice Variant

PurposeThis study aimed to evaluate the prognostic role of AR-V7 in terms of prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) in CRPC patients treated with novel hormonal therapy (NHT) (Abiraterone and Enzalutamide) or taxane-based chemotherapy (Docetaxel and Cabazitaxel).MethodsA comprehensive literature search was conducted on PubMed, Embase, and the Web of Science from inception to February 2020. Studies focusing on the prognostic values of AR-V7 in CRPC patients treated with NHT or chemotherapy were included in our meta-analysis. The OS and PFS were analyzed based on Hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, Odds ratios (ORs) and 95% CIs were summarized for the AR-V7 conversion after treatment and the PSA response.ResultsThe AR-V7 positive proportion increased significantly after NHT treatment (OR 2.56, 95% CI 1.51–4.32, P<0.001), however, it declined after chemotherapy (OR 0.51, 95% CI 0.28–0.93, P=0.003). AR-V7-positive patients showed a significantly decreased PSA response rate after NHT (OR 0.13, 95% CI 0.09–0.19, P<0.001) but not statistically significant for chemotherapy (OR 0.63, 95% CI 0.40-1.01, P=0.06). Notably, PFS (HR 3.56, 95% CI 2.53–5.01, P<0.001) and OS (HR 4.47, 95% CI 3.03–6.59, P<0.001) were worse in AR-V7-positive ttreated with NHT. Similarly, AR-V7 positivity correlated with poor prognosis after chemotherapy as evidenced by shorter OS (HR 1.98, 95% CI 1.48-2.66, P<0.001) and a significantly shorter PFS (HR 1.35, 95% CI 0.97-1.87, P=0.07).ConclusionNHT treatment increased AR-V7 positive proportion whereas chemotherapy decreased it. Moreover, AR-V7 positivity correlated with lower PSA response, poorer PFS, and OS in CRPC treated with NHT, and shorter OS in patients receiving chemotherapy.

The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 308-308
Author(s):  
Onal Cem ◽  
Ali Murat Sedef ◽  
Fatih KOse ◽  
Ezgi Oymak ◽  
Ozan Cem Guler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Characteristic Analysis ◽  
Lymphocyte Ratio ◽  
Castration Resistant ◽  
Psa Response

308 Background: The aim of this study is to evaluate the prognostic implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and after 4 and 12 weeks of treatment with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively evaluated 102 mCRPC treated with abiraterone either pre- or post-chemotherapy between November 2012 and October 2017 in three institutions. We calculated NLR and PLR at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks. Fifty patients (49%) were treated with abiraterone post-docetaxel, and 52 patients (51%) received abiraterone pre-chemotherapy. Based on receiver operating characteristic analysis, patients were stratified as low NLR ( < 3.1) or high NLR (≥ 3.1), and low PLR ( < 163) or high PLR (≥ 163). The cutoff for anemia was < 12g/dL. Results: Median follow-up times for patients overall and for those who survived were 24.0 months (range, 0.3 – 54.9 months) and 25.5 months (range, 2.8 – 54.9 months), respectively. The median time of abiraterone treatment was 8.1 months (range, 2.4 – 40.1 months). The median overall survival (OS) was 20.8 months (interquartile range: 17.3–24.4). In univariate analysis, NLR, PLR, PSA response, and low hemoglobin (Hgb) were found significantly predictive of OS and progression-free survival (PFS). In multivariate analysis, declines in NLR and PSA of ≥ 90% emerged as significant independent predictors of OS and PFS. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. Patients with baseline Hgb > 12 g/dL had significantly longer median OS compared with patients with Hgb ≤ 12 g/dL; however, the significance of Hgb was lost at 12 weeks. Conclusions: NLR and PSA response to abiraterone was a significant predictor of OS and PFS in mCRPC patients treated with abiraterone delivered either pre- or post-chemotherapy. Furthermore, persistent increase in NLR during abiraterone has prognostic value for OS in patients with mCRPC.

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.

scholarly journals Efficacy and safety of novel treatments in chemotherapy-naïve castration-resistant prostate cancer

2020 ◽  
Author(s):  
ZhiChao Min
Keyword(s):  
Prostate Cancer ◽  
Random Effects ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Novel Treatments ◽  
Castration Resistant ◽  
Hazard Ratios ◽  
Meta Analyses

Abstract Background: Currently, novel treatment methods for chemotherapy-naïve castration-resistant prostate cancer (CRPC) patients have been applied in clinical practice. Since the optimum regimen remains inconclusive, this study compares the efficacy and safety of these treatments by network meta-analysis. Methods: The PubMed and ClinicalTrials.gov database and review articles before January 30, 2020 were searched and date were extracted. A total of 29908 patients with CRPC from 23 randomized controlled trials were included. Relative hazard ratios (HR) had been used to assess the effects on overall survival (OS), progression-free survival (PFS) or radiographic PFS (rPFS), and adverse events (AEs). We then pooled the data and used Bayesian and frequentist random-effects model to identify the best treatment strategy. Results: Compared with the placebo, both Bayesian and frequentist random-effects network meta-analyses found that only enzalutamide and abiraterone had a significant effect in OS. Similar results were observed in PFS/rPFS. Bicalutamide, tasquinimod and orteronel could also improve rPFS. Enzalutamide only could improve rPFS more effectively than abiraterone with no significant differences in OS/PFS/AEs. In any subgroups of patients with age <75, ≥75 or ECOG score = 0,1 or Gleason score ≤7, ≥8, enzalutamide could improve the OS significantly. Nevertheless, the significant benefit of abiraterone was only found in patients with age <75 and ECOG score = 0.Conclusions: Our network analysis suggested that both enzalutamide and abiraterone are optimal treatment for chemotherapy-naïve CRPC patients with age <75 and ECOG score = 0 for great improvement on OS and PFS. In addition, enzalutamide is also an optimum therapy for chemotherapy-naïve CRPC patients with age ≥75 and ECOG score = 1.

A phase IV, randomized, double-blind, placebo (PBO)-controlled study of continued enzalutamide (ENZA) post prostate-specific antigen (PSA) progression in men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5004-5004 ◽  
Author(s):  
Gerhardt Attard ◽  
Michael Borre ◽  
Howard Gurney ◽  
Yohann Loriot ◽  
Corina Andresen ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Progression Free Survival ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Synthesis Inhibitor ◽  
Double Blind ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

5004 Background: We hypothesized resistance to the androgen receptor inhibitor ENZA is due to increases in androgens and can be overcome by combination with the androgen synthesis inhibitor abiraterone (abi). The phase 4 PLATO trial (NCT01995513) is evaluating the safety and efficacy of continued ENZA + abi/prednisone (abi/P) vs PBO + abi/P after PSA progression on ENZA. Methods: In Period (P) 1, men with chemotherapy-naïve mCRPC received ENZA (160 mg); men with no PSA increase from baseline at wk 13 and 21 continued treatment until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir). Eligible men were then randomized 1:1 in P2 to ENZA + abi/P (1000 mg/10 mg) or PBO + abi/P. The primary endpoint (EP) was progression-free survival (PFS; radiographic or unequivocal clinical progression, or death on study) in P2, with a prespecified sensitivity analysis of radiographic PFS (rPFS); protected secondary EPs were time to PSA progression (TTPP) and PSA response ≥ 50% in P2. Results: 509 men enrolled in P1. At data cutoff (Oct 7, 2016), 84 were active, 174 discontinued, and 251 were randomized in P2 (ENZA + abi/P, n = 126; PBO + abi/P, n = 125). Median treatment duration in P2 was 5.6 mo for both arms. PFS event by radiographic/clinical/death was 38%/25%/2% for ENZA + abi/P and 55%/18%/1% for PBO + abi/P. Median PFS was 5.7 mo for ENZA + abi/P and 5.6 mo for PBO + abi/P (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.61, 1.12; P = 0.22). Median TTPP was 2.8 mo for both arms (HR, 0.87; 95% CI, 0.62, 1.24; P = 0.45). PSA response rate was 0.8% for ENZA + abi/P and 2.5% for PBO + abi/P ( P = 0.31). Median rPFS was 10.0 mo for ENZA + abi/P and 7.0 mo for PBO + abi/P (HR, 0.67; 95% CI, 0.47, 0.94; P = 0.02). The most common (≥ 15%) adverse events for ENZA + abi/P vs PBO + abi/P were back pain (21% vs 23%), hypertension (20% vs 7%), nausea (17% vs 9%), and fatigue (14% vs 15%). Conclusions: ENZA + abi/P post PSA progression on ENZA was associated with increased hypertension and nausea and did not result in a statistically significant improvement in composite PFS. The signal seen in rPFS needs further evaluation. Clinical trial information: NCT01995513.

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 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.

Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer

2009 ◽  
Vol 27 (15) ◽  
pp. 2429-2435 ◽  
Author(s):  
Karim Fizazi ◽  
Philippe Beuzeboc ◽  
Jean Lumbroso ◽  
Vincent Haddad ◽  
Christophe Massard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Psa Relapse ◽  
Castration Resistant ◽  
Psa Response ◽  
Grade 3

PurposeTo assess docetaxel combined with samarium-153–ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC).Patients and MethodsPatients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m2/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA–progression-free survival (PFS) as the primary end point.ResultsForty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel–samarium-153–EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%).ConclusionCombining docetaxel and samarium-153–EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

scholarly journals Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

2020 ◽  
Vol 25 (11) ◽  
pp. 1892-1900 ◽  
Author(s):  
Keiichiro Mori ◽  
Hadi Mostafaei ◽  
Benjamin Pradere ◽  
Reza Sari Motlagh ◽  
Fahad Quhal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Credible Interval ◽  
Tolerability Profile ◽  
Castration Resistant Prostate Cancer ◽  
Eligibility Criteria ◽  
Castration Resistant

Abstract Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77–0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78–0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69–0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74–0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

Multicenter prospective study of switching from GnRH agonists to GnRH antagonist for patients with early stage of castration resistant prostate cancer as a second-line hormonal therapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 183-183
Author(s):  
Yumiko Yokomizo ◽  
Narihiko Hayashi ◽  
Akitoshi Takizawa ◽  
Kazuki Kobayashi ◽  
Jun-ichi Ohta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gnrh Agonist ◽  
Hormonal Therapy ◽  
Gnrh Antagonist ◽  
Early Stage ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response

183 Background: It was reported that GnRH antagonist could extend progression free survival for prostate cancer patients significantly longer than GnRH agonist in a first line hormonal therapy. However, the usefulness of switching from GnRH agonist to GnRH antagonist as a second hormonal therapy remains obscure. We performed a multicentral prospective study to investigate whether the switching from GnRH agonist to GnRH antagonist (degalerix) for patients with castration resistant prostate cancer (CRPC) as the 2nd line hormonal therapy was effective. Methods: 37 patients who were pathologically diagnosed as prostatic adenocarcinoma and developed CRPC after 1st line hormonal therapy with GnRH agonist plus anti-androgens were enrolled. After confirming anti-androgen withdrawal syndrome, they were treated with switching from GnRH agonists to degalerix. The primary endpoint was PSA response (PSA decline or up to 10% over baseline PSA). Secondary endpoints were the time to 25% PSA increase from the baseline (PSA response time), PSA progression free survival (PPFS), the time to treatment failure, cancer specific survival, radiographic PFS (rPFS), and safety. Results: Mean age was 76 years old, super high risk; 20 cases (54.1%), high risk; 11 cases (29.7%), intermediate risk; 5 cases (13.5%), low risk; one case (2.7%). PSA responder rate was 24.3% (9 cases). In responders, the median PSA response time was 5.75 months, the median PPFS was 1.77 months, and rPFS rate at 3 months was 96%. Regarding safety, only 2 cases (5.4%) showed G3 of AE. The PSA response had no relationship with the change of serum testosterone, LH nor FSH. Conclusions: The effectiveness of switching from GnRH agonist to GnRH antagonist showed to be limited. Although no predictive factor of the switching was recognized, some long-term responders were seen. We expect the possibility of switching to GnRH antagonist for patients in the early stage of CRPC, especially non-metastatic status. Clinical trial information: UNKNOWN.

scholarly journals Efficacy and safety of novel treatments in chemotherapy-naïve castration-resistant prostate cancer

2020 ◽  
Author(s):  
ZhiChao Min
Keyword(s):  
Prostate Cancer ◽  
Random Effects ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Novel Treatments ◽  
Castration Resistant ◽  
Hazard Ratios ◽  
Meta Analyses

Abstract Background Currently, novel treatment methods for chemotherapy-naïve castration-resistant prostate cancer (CRPC) patients have been applied in clinical practice. Since the optimum regimen remains inconclusive, this study compares the efficacy and safety of these treatments by network meta-analysis. Methods The PubMed and ClinicalTrials.gov database and review articles before January 30, 2020 were searched and date were extracted. A total of 29908 patients with CRPC from 23 randomized controlled trials were included. Relative hazard ratios (HR) had been used to assess the effects on overall survival (OS), progression-free survival (PFS) or radiographic PFS (rPFS), and adverse events (AEs). We then pooled the data and used Bayesian and frequentist random-effects model to identify the best treatment strategy. Results Compared with the placebo, both Bayesian and frequentist random-effects network meta-analyses found that only enzalutamide and abiraterone had a significant effect in OS. Similar results were observed in PFS/rPFS. Bicalutamide, tasquinimod and orteronel could also improve rPFS. Enzalutamide only could improve rPFS more effectively than abiraterone with no significant differences in OS/PFS/AEs. In any subgroups of patients with age <75, ≥75 or ECOG score = 0,1 or Gleason score ≤7, ≥8, enzalutamide could improve the OS significantly. Nevertheless, the significant benefit of abiraterone was only found in patients with age <75 and ECOG score = 0. Conclusions Our network analysis suggested that both enzalutamide and abiraterone are optimal treatment for chemotherapy-naïve CRPC patients with age <75 and ECOG score = 0 for great improvement on OS and PFS. In addition, enzalutamide is also an optimum therapy for chemotherapy-naïve CRPC patients with age ≥75 and ECOG score = 1.

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