Prospective evaluation of the response to prednisone-dexamethasone switch in castration-resistant prostate cancer patients treated with abiraterone pre- and post-docetaxel.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 327-327 ◽  
Author(s):  
Nuria Romero-Laorden ◽  
Elena Castro ◽  
Rebeca Lozano ◽  
M Isabel Sáez ◽  
Jeannette Valero ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Biochemical Progression ◽  
Bone Scans ◽  
Lymph Metastasis

327 Background: Abiraterone acetate (AA) administered with prednisone (P) to reduce mineralocorticoid-related adverse events improves survival in CRPC with a favourable tolerance profile. However, in the phase I/II of AA without steroids, dexamethasone 0,5mg/day was added after biochemical progression reaching a 25% of PSA decline. Lorente et al (BJC, 2014) showed durable biochemical responses in 40% of cases treated with AA and steroid switch in the post-docetaxel setting. We hypothesize that P to D switch in patients with biochemical progression to AA+P would lead to secondary responses also in the pre-docetaxel setting. Methods: Change of P 5mg/12h to D 0.5mg/24h was prospectively tested in clinically stable CRPC with biochemical progression ( > 25% PSA rise over nadir, confirmed in a second determination) and/or limited radiological progression ( < 3 new bone/lymphatic metastasis, non-bulky), after ³12 weeks of AA+P. PSA was monitored q4wks. CT- & bone-scans were performed every 12-16 weeks. Biochemical and radiological responses were evaluated by PSAWG2 and RECIST criteria. Survival outcomes were calculated using Kaplan-Meier method. Results: 18 patients were included (11 pre- & 7 post-docetaxel). Median age 72 (60-85); visceral, bone and/or lymph metastasis were present in 17%, 83% and 50% of patients. Median PSA at AA+P and AA+D commencement was 81 ng/ml and 100ng/ml, respectively. Biochemical response was observed in 83% of patients: 56% with a PSA decrease ≥ 30%, and 28% with PSA decrease ≥ 50%. Median biochemical progression-free survival (bPFS) with AA+P was 5.7 months (CI95% 2.9-9.1) and 3.8m (CI95% 1.4-6.5) in the pre- and post-docetaxel setting, respectively. Median bPFS with AA+D was 5.4m (1.2-8.8) and 2.5 (CI95% 1.1-2.9) in the pre- and post-docetaxel settings. Two radiological partial responses were observed with AA+D. Conclusions: Clinically stable patients with limited disease progression after AA+P may benefit from steroid switch in both the pre- and post-docetaxel settings.

The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 133-133
Author(s):  
Yuchao Ni ◽  
Jinge Zhao ◽  
Junru Chen ◽  
Guangxi Sun ◽  
Sha Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression ◽  
Biochemical Progression ◽  
First Line Treatment

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.

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.

scholarly journals Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhenyu Yang ◽  
Yuchao Ni ◽  
Diwei Zhao ◽  
Yijun Zhang ◽  
Jun Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Prognostic Predictors ◽  
Castration Resistant ◽  
Risk Stratification Tool ◽  
Psa Response ◽  
Biochemical Progression

Abstract Background To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P). Methods Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety. Results One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS. Conclusions A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

Results of subset analyses on overall survival (OS) from study CA184-043: Ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Charles G. Drake ◽  
Eugene D. Kwon ◽  
Karim Fizazi ◽  
Alberto Bossi ◽  
Alfons JM van den Eertwegh ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Prognostic Features ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
To Receive ◽  
Clinical Trial Information

2 Background: The CA184-043 phase 3 study did not reach statistical significance for its primary endpoint of OS (HR=0.85, p=0.053). However, antitumor activity was observed in other efficacy endpoints, including progression-free survival. Prespecified subset analyses were performed to understand if any prognostic features may identify mCRPC patients (pts) more likely to benefit from Ipi treatment. Methods: 799 pts were randomized to receive a single dose of radiotherapy (RT) followed by either Ipi (N=399) or Pbo (N=400). Prespecified subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Prespecified subset analyses suggested that Ipi may be more active in pts with favorable prognostic factors, including no visceral disease, alkaline phosphatase <1.5 ULN, and hemoglobin ≥11 g/dL (Table). The safety profile in this study was consistent with previous reports of Ipi. Conclusions: Based on these subset analyses, Ipi added to RT appears to have greater activity than RT alone in pts with a favorable prognostic profile. These results support continued investigation of Ipi in the ongoing CA184-095 study in chemotherapy-naive mCRPC pts. Clinical trial information: NCT00861614. [Table: see text]

Clinical significance of AR mRNA quantification from circulating tumor cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone (Abi) or enzalutamide (Enza).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 132-132 ◽  
Author(s):  
John Silberstein ◽  
Brandon Luber ◽  
Hao Wang ◽  
Changxue Lu ◽  
Yan Chen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Continuous Variable ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Mrna Quantification ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression

132 Background: AR-targeting agents remain the backbone of mCRPC therapy. We previously reported an association between AR-V7 mRNA detection in CTCs and resistance to Abi/Enza (NEJM 2014). Here, we report the prognostic significance of full-length androgen receptor (AR-FL) mRNA quantification from CTCs in pts starting Abi or Enza. Methods: We prospectively enrolled mCRPC pts starting Abi or Enza, and examined the prognostic value of AR-FL detection using a CTC-based mRNA assay (modified AdnaTest, Qiagen). We examined PSA50 responses, PSA progression free survival (PSA-PFS), clinical/radiologic PFS (PFS), and overall survival (OS). We constructed multivariable (MVA) Cox regression models adjusting for AR-V7 status, PSA level, Gleason sum, number of prior therapies, prior Abi/Enza use, prior taxane use, presence of visceral disease, and ECOG score. Results: We enrolled 202 pts (median f/u 12.9 mo). AR-FL status was negative in 97/202 pts (48%), < median in 52/202 (26%) and > median in 53/202 (26%). Higher AR-FL levels correlated with positive AR-V7 detection (35.5 copies [range: 2.5–1209] in AR-V7+ vs 1.4 copies [range: 0–172.5] in AR-V7–, P< .001), as well as lower PSA50 responses (55.4 copies in nonresponders vs 6.7 copies in responders, P< .001). In Kaplan-Meier analysis, PSA-PFS, PFS and OS differed significantly between AR-FL negative, AR-FL < median, and AR-FL > median (Table). In MVA models, AR-FL level (as a continuous variable) was prognostic for PSA-PFS (HR 1.06, 95%CI 1.00–1.12, P= .04) and trended with prognosis for PFS (HR 1.04, 95%CI 0.99–1.11, P= .13) and OS (HR 1.07, 95%CI 1.00–1.15, P= .06). AR-V7 status was also independently prognostic for all outcomes in MVA analyses. Conclusions: This study demonstrates CTC-derived AR-FL copy number is prognostic for clinical outcomes in Abi/Enza-treated mCRPC pts. In addition to AR-V7 status, AR-FL quantification could serve as another molecular biomarker of Abi/Enza sensitivity after analytical validation/standardization. [Table: see text]

Immunological and genomic correlates of response to anti-PD1 checkpoint therapy in mismatch proficient and deficient patients with metastasized castration resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 248-248 ◽  
Author(s):  
Minke Smits ◽  
Maarten Johannes van der Doelen ◽  
Harm Westdorp ◽  
Inge M. van Oort ◽  
Michiel Sedelaar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Computational Prediction ◽  
Cell Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Free Survival ◽  
Immune Correlates ◽  
Castration Resistant ◽  
Immune Oncology

248 Background: Response to anti-PD1/PDL1 checkpoint therapy has been witnessed in only a minority of patients with castration-resistant prostate cancer (CRPC). Microsatellite instability (MSI) is the only biomarker predictive of response; additional immune and genomic correlates are needed to improve the proportion of patients that may benefit from checkpoint immunotherapy. Methods: CRPC patients were treated with anti-PD1 checkpoint immunotherapy in two basket-studies, depending on PDL1-positivity ( > 1%) or presence of MSI, and consented to prospective immune-oncology biomarker study. Genomic and immune correlates of response were studied in both MSI as microsatellite stable CRPC patients, and included PDL1 expression , whole genome sequencing on a baseline fresh metastatic biopsy, tumor microenvironment (immuno)profiling using multi-color immunohistochemistry, computational prediction of neoantigens, T-cell receptor sequencing and MHC-tetramer staining. Response was evaluated according to PCWG3 criteria and treatment was continued until radiological progression with lack of clinical benefit or toxicity. Results: At present 11 CRPC patients were included in the program and treated with nivolumab (n = 4) and pembrolizumab (n = 7). Treatment is currently ongoing in 7/11 (64%) of patients, with treatment discontinuation due to immune-related colitis (n = 2) and disease progression (n = 2). Biochemical PSA ( > 50%) responses were seen in both MSI and PDL1 positive patients. Median progression-free survival has not yet been reached. Translational studies on genomic and immune correlates of response will be presented in detail. Conclusions: Encouraging responses to anti-PD1 checkpoint immunotherapy were seen in CRPC patients selected for PDL1-positivity and MSI. An integrative biomarker suite will likely be needed to predict response to anti-PD1 therapy in CRPC.

Sign in / Sign up

Export Citation Format

Share Document