scholarly journals RNA Biomarkers as a Response Measure for Survival in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6279
Author(s):  
Emmy Boerrigter ◽  
Guillemette E. Benoist ◽  
Inge M. van Oort ◽  
Gerald W. Verhaegh ◽  
Anton F. J. de Haan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prediction Model ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Added Value ◽  
Clinical Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Rna Biomarkers

Treatment evaluation in metastatic castration-resistant prostate cancer is challenging. There is an urgent need for biomarkers to discriminate short-term survivors from long-term survivors, shortly after treatment initiation. Thereto, the added value of early RNA biomarkers on predicting progression-free survival (PFS) and overall survival (OS) were explored. The RNA biomarkers: KLK3 mRNA, miR-375, miR-3687, and NAALADL2-AS2 were measured in 93 patients with mCRPC, before and 1 month after start of first-line abiraterone acetate or enzalutamide treatment, in two prospective clinical trials. The added value of the biomarkers to standard clinical parameters in predicting PFS and OS was tested by Harell’s C-index. To test whether the biomarkers were independent markers of PFS and OS, multivariate Cox regression was used. The best prediction model for PFS and OS was formed by adding miR-375 and KLK3 (at baseline and 1 month) to standard clinical parameters. Baseline miR-375 and detectable KLK3 after 1 month of therapy were independently related to shorter PFS, which was not observed for OS. In conclusion, the addition of KLK3 and miR-375 (at baseline and 1 month) to standard clinical parameters resulted in the best prediction model for survival assessment.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

scholarly journals Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study

2020 ◽  
Author(s):  
K Kobayashi ◽  
N Okuno ◽  
G Arai ◽  
H Nakatsu ◽  
A Maniwa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant

Abstract Aim The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. Methods Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon’s minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. Results For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55–86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4–84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%–69.3%), median prostate-specific antigen–progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). Conclusions Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen–progression-free survival was shorter than that reported in previous studies. Considering the benefit–risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

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 Androgen Receptor Targeted Therapy + Radiotherapy in Metastatic Castration Resistant Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Maria Massaro ◽  
Giuseppe Facondo ◽  
Gianluca Vullo ◽  
Anna Maria Aschelter ◽  
Alessandro Rossi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Progression Free Survival ◽  
Conformal Radiotherapy ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant

ObjectivesTo investigate whether radiotherapy as metastasis-directed therapy (MDT) on oligo-progressive sites in metastatic castration-resistant prostate cancer (mCRPC) patients during treatment with androgen receptor-targeted therapy (ARTT) may lead to control resistant lesions, prolonging ARTT. We analysed progression free survival, overall survival and prognostic parameters that can identify patients that best suit to this approach.Patients and MethodsRetrospective analysis of a total of 67 lesions in 42 mCRPC patients treated with ablative or palliative RT to oligoprogressive lesions during ARTT. Twenty-eight patients (67%) underwent ARTT with Abiraterone acetate and 14 patients (33%) underwent ARTT with Enzalutamide. Median time between the start of ADT and ARTT beginning was 50.14 months (range 3.37-219 months). We treated 58 lesions (87%) with 3D conformal radiotherapy (3DCRT) and nine lesions (13%) with stereotactic body radiotherapy (SBRT). The Kaplan Meier method was used to assess the median overall survival (OS) and the progression-free survival (PFS).ResultsMedian follow-up was 28 months (range 3-82 months). Median OS was 32.5 months (95% CI 25.77-39.16), 1 and 2-year OS were 71.6% and 64.1%, respectively. Median PFS was 19,8 months (95% CI 11.34–28.31), 1 and 2-year PFS were 67.2% and 47.4%, respectively. Median OS for patients that underwent radiotherapy before 6 months from the start of ARTT was 23.4 months (95% CI 2.04-44.89) and 45.5 months (95% CI 31.19-59.8) for patients that underwent radiotherapy after 6 months (p = 0.009).ConclusionLocal ablative radiation therapy directed to progressive metastasis is a non-invasive, well tolerated treatment with efficacy on prolonging clinical benefit of systemic therapies with ARTT. Patients who underwent RT &gt;6 months from the start of ARTT presented a statistically better OS and PFS compared with patients who underwent radiotherapy &lt;6 months from the start of ARTT.

Prediction of favorable outcome in a docetaxel rechallenge setting in metastatic castration-resistant prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 68-68
Author(s):  
Matthias Michael Heck ◽  
Mark K. Thalgott ◽  
Margitta Retz ◽  
Petra Wolf ◽  
Tobias Maurer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Oncological Outcome ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Treatment Variable ◽  
Castration Resistant ◽  
Line Chemotherapy

68 Background: To identify predictors of favourable oncological outcome in metastatic castration-resistant prostate cancer (mCRPC) patients who are treated with docetaxel rechallenge following first-line chemotherapy with docetaxel. Methods: We retrospectively evaluated the oncological outcome of mCRPC patients who were treated with 3-weekly docetaxel (75mg/m2) at first-line chemotherapy and rechallenge plus prednisone/ prednisolone. The endpoints of oncological outcome were PSA-progression-free survival (PSA-PFS) and overall survival (OS) after initiation of docetaxel rechallenge. The effect of clinical variables on PSA-PFS and OS was statistically analysed by a log-rank test or Cox regression with hazard ratios. All analyses were performed using a 0.05 level of significance. Results: 47 patients were included on analysis. At a median follow-up of 25.8 months (range 9.8-89.8 months) after the first administration of docetaxel, 27 (57.4%) patients had died. Median PSA-PFS was 5.9 months (95% CI 3.5-6.8 months) and median OS was 21.4 months (95% CI 18.9-23.9 months) after initiation of docetaxel rechallenge. PSA-reduction ≥ 30% was the only pre-treatment variable that correlated significantly with prolonged PSA-PFS (p=0.03) and OS (p=0.002). Patients with PSA-reduction ≥ 30% at first-line chemotherapy showed a median OS of 21.8 months since initiation of docetaxel rechallenge in comparison to 4.5 months in patients with < 30% PSA-reduction. Conclusions: Docetaxel rechallenge represents an active treatment option in selected docetaxel-pretreated patients with mCRPC. In this retrospective study, PSA-reduction ≥ 30% at first-line chemotherapy with docetaxel predicted superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.

Metabolic syndrome in castration-resistant prostate cancer patients treated with abiraterone.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 213-213
Author(s):  
Vincenza Conteduca ◽  
Orazio Caffo ◽  
Lisa Derosa ◽  
Antonello Veccia ◽  
Elisabetta Petracci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metabolic Syndrome ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Increased Risk ◽  
Hormonal Therapies ◽  
The Impact

213 Background: The presence and the impact of metabolic syndrome (MS) in castration-resistant prostate cancer (CRPC) men treated with novel hormonal therapies, as abiraterone, has not still been studied. The study aims to assess the impact of MS on progression free survival (PFS) and overall survival (OS) from time starting abiraterone. Methods: We retrospectively evaluated a consecutive series of metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the time of initiation of abiraterone, during treatment and follow-up. Cox regression model was used to evaluate the role of MS on the two end-points. Results: One hundred seventy eight patients had sufficient data to assess the presence of MS. Mean age (± SD) at start of abiraterone was 74.0 ± 7.7 years. Seventy out of 178 patients (39.5%) met MS criteria at baseline, before abiraterone initiation, whereas for eleven patients this occurred during treatment. Median PFS was equal to 5 months for patients with MS versus 9 months for those without MS. Patients with MS had a 2-fold increased risk of progression or death for all causes than patients without MS (HR=1.9, 95% CI [1.3-2.7], P<0.001). Median OS was 16 months and 22 months in patients with and without MS, respectively. After adjusting for covariates, MS resulted not significantly associated to OS (HR=1.2, 95% CI [0.8-1.9], P=0.340). Conclusions: MS may represent a complication of patients treated with abiraterone. The presence of MS appears to be a risk factor for shorter PFS in patients with CRPC treated with abiraterone, even if it does not show any impact on OS, so it needs a further prospective evaluation.

Association of single nucleotide polymorphisms (SNPs) in CYP17A1 and SLCO2B1 genes and clinical outcome in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: results of the ABIGENE prospective study.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 358-358
Author(s):  
Delphine Borchiellini ◽  
Hakim Mahammedi ◽  
Julien Viotti ◽  
Gwenaelle Gravis ◽  
Guilhem Roubaud ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcome ◽  
Response Rate ◽  
Cox Regression ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Pharmacogenetic Study ◽  
Castration Resistant ◽  
Psa Response ◽  
The Impact

358 Background: Abiraterone acetate (AA), a CYP17A1 inhibitor, has been approved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Germline polymorphisms in genes involved in androgen biosynthesis or transport may influence response and survival in this setting. Methods: ABIGENE is a multicentric prospective non-randomized pharmacogenetic study (NCT01858441). The primary objective was to investigate the association between 13 SNPs in genes related to AA pharmacology (CYP17A1, SLCO2B1 and SLCO2B3) and radiographic progression-free survival (rPFS), according to PCWG2 criteria, in pts with mCRPC treated with first-line AA + prednisone. The main secondary objectives were to evaluate the impact of these SNPs on radiographic and PSA response, overall survival (OS) and toxicity. SNPs were detected in blood samples before starting AA and analyzed by pyrosequencing or PCR-RFLP methods. Kaplan-Meyer’s curves with log-rank tests and cox regression models were used to identify relationships between SNPs and survival. Chi2 tests and student t-tests were used to identify association with response rate and toxicity. Results: 147 pts in 17 french centers were included between 2013 and 2017. Here are presented the results for the first 109 pts. The median follow-up was 28.7 months. Overall response rate (ORR) was 17%, and 74% pts had stable disease as the best response. Median rPFS was 10.9 months (95% CI 9.2-15.3). One SNP (rs10883782) in CYP17A1 was associated with rPFS on AA therapy (Table). Two other SNPs in CYP17A1 (rs4919683) and SLCO2B1 (rs1077858) were significantly associated with radiographic response. Data on PSA response, OS and toxicity will be presented at the meeting. Conclusions: This is the first prospective dedicated study to show an association between SNPs related to androgen metabolism and clinical outcome in mCRPC treated with AA. Clinical trial information: NCT01858441. [Table: see text]

Abiraterone acetate plus prednisone/prednisolone compared with enzalutamide in metastatic castration resistant prostate cancer before or after chemotherapy: A retrospective study of real-world data (ACES).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 303-303
Author(s):  
Prantik Das ◽  
James Price ◽  
Michael Jones ◽  
Cristina Martin-Fernandez ◽  
Akram Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Significant Difference ◽  
Biochemical Progression

303 Background: Abiraterone acetate (a prodrug of abiraterone, which is a selective inhibitor of androgen biosynthesis) combined with prednisone/prednisolone (AA+P) and enzalutamide (ENZ) (an androgen-receptor–signalling inhibitor) have proven survival benefit in men with metastatic castration resistant prostate cancer (mCRPC) in chemo naïve and prior chemo patients. There have been no studies directly comparing the effectiveness of ENZ to AA+P in mCRPC patients. Methods: A retrospective, survival analysis study of 143 real world mCRPC patients (90 in AA+P and 53 in ENZ group) was conducted. Patients who started their treatment between 1st February 2012 and 31st May 2016 were included. The primary endpoint was biochemical progression free survival (PFS). Secondary end points were radiographic progression free survival (rPFS) and overall survival (OS). Data was analysed using Cox proportional hazards models, adjusting for covariates: prior radical or palliative treatment; Gleason score; baseline PSA; age; and chemo naïve or not. Results: After median follow up of 15 months (IQR 7 to 23) 112 events of biochemical progression were observed (71 in AA+P and 41 in ENZ). 41%in AA+P group and 30% patients in ENZ group received prior chemo. The chance of biochemical progression was significantly lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (Hazard Ratio 0.54, 95% CI 0.35 to 0.82, p=0.004. There was a trend implying the chance of rPFS could be higher among ENZ patients than AA+P patients (HR 1.24, 95% CI 0.76 to 2.02, p=0.4). OS is lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (HR 0.91, 95% CI 0.59 to 1.41, p=0.7). 38% of ENZ patients reported fatigue compared to 16% of AA+P patients while hypertension was reported slightly more in AA+P patients than in ENZ patients. Conclusions: This study showed a statistically significant difference in biochemical progression-free survival, favouring ENZ, but no significant difference in radiographic progression-free survival or overall survival.

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