Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel (D).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 146-146
Author(s):  
Avivit Peer ◽  
Maya Ish-Shalom ◽  
Natalie Maimon ◽  
Maya Gottfried ◽  
Ben Boursi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Risk Category ◽  
Appendicular Skeleton ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Disease Extent ◽  
Free Survival ◽  
Psa Response

146 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to deocetaxel. It is a potent and selective CYP 17 inhibitor that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D. Methods: Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease ≥50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/ neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023). Conclusions: In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.

Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) refractory to docetaxel (D).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16068-e16068
Author(s):  
Avivit Peer ◽  
Maya Ish-Shalom ◽  
Natalie Maimon ◽  
Maya Gottfried ◽  
Ben Boursi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Risk Category ◽  
Appendicular Skeleton ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Disease Extent ◽  
Free Survival ◽  
Psa Response

e16068 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to D. It is a potent and selective CYP 17 inhibitor, that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. Aims: To compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D. Methods: Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease ≥50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023). Conclusions: In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.

Comparison of abiraterone acetate (Abi) versus ketoconazole (Keto) in chemotherapy-naive patients (CN-pts) with metastatic castration resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 260-260
Author(s):  
Avivit Peer ◽  
Avivit Neumann ◽  
Avishay Sella ◽  
Eli Rosenbaum ◽  
Victoria Neiman ◽  
...  
Keyword(s):  
Clinical Data ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Clinical Effectiveness ◽  
Axial Skeleton ◽  
Risk Category ◽  
Appendicular Skeleton ◽  
Castration Resistant Prostate Cancer ◽  
Disease Extent ◽  
Psa Response

260 Background: Abi is a standard treatment (tx) in CN-pts with mCRPC. It is a potent and selective CYP 17 inhibitor. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17. Clinical data (Peer et al, Prostate 2014) suggests that in docetaxel (D) refractory mCRPC, the outcome of abi tx may be superior to keto. However, there are limited clinical data comparing both agents in CN-pts with mCRPC. We aimed to compare the clinical effectiveness of abi vs keto in CN-pts with mCRPC, who were treated after the year 2004 (approval of D for the tx of mCRPC). Methods: Records from 72 CN-pts with mCRPC treated with abi in 5 Israeli centers were reviewed retrospectively, and matched by pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012) to pts treated with keto 200 - 400 mg 3x day (international database, n = 156, from 4 centers across the US and Israel). We compared the PSA response (decrease ≥ 50% from baseline), biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. Results: The groups were matched by pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012), based on pretreatment NLR and PSA doubling time, and the prior response to a gonadotropin-releasing hormone agonist. The groups were balanced regarding age (72 abi vs 70 keto), time from primary tx to disease relapse, gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), and ECOG PS. In the groups of abi vs keto, PSA response was 75% vs 47% (OR 3.8, p = 0.04), median biochemical PFS 12 vs 6 months (HR 0.62, p = 0.03), median radiological PFS 16 vs 8 months (HR 0.54, p = 0.01), median OS not reached after a median follow-up time of 18 months vs 26 months, and tx interruption d/t adverse events 10% vs 22% (0R 0.65, p = 0.05). Conclusions: In CN-pts with mCRPC, the outcome of pts treated with abi may be superior to keto.

Association of androgen receptor (AR) gene status in plasma DNA with outcome on enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC): Exploratory results from the PREMIERE trial—On behalf of SOGUG.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5016-5016
Author(s):  
Enrique Grande ◽  
Albert Font Pous ◽  
Natalia Fernández Núñez ◽  
Aranzazu Gonzalez del Alba ◽  
Begoña Mellado ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Digital Pcr ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Dna ◽  
Free Survival ◽  
Exact Test ◽  
Road Map ◽  
Psa Response ◽  
Gene Status

5016 Background: Building on previous discoveries studying AR status in plasma (Carreira S, Sci Transl Med 2014, Romanel A, Sci Transl Med 2015) and following a road-map for biomarker development, we aimed to clinically qualify AR status in chemotherapy-naïve mCRPC using an optimized multiplex droplet digital PCR (ddPCR) assay (Condeduca et al.;ASCO2017;Abstract#). Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC patients were recruited in 16 Spanish hospitals. Tissue and blood samples were required at study entry. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma ARand CTC characterization (Grande E. ESMO 2016 & Font A. et al; ASCO2017; Abstract #). Outcome measures included PSA-progression-free survival (sPFS), radiographic progression-free survival (rPFS) and overall survival (OS). Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-four patients had plasma DNA available for analysis. At baseline, AR gain was present in 11 pts (12%) and CTCs in 35 (37%). AR gain in CTC-positive and negative patients was 20% and 7%, respectively. At first interim analysis and with a median follow-up of 10.6 months, detection of AR gain was associated with worse sPFS (median, 3.60 versus 15.5 m, HR, 4.33; 95% CI 1.94-9.68; P < 0.001), rPFS (median, 3.90 m versus not reached HR, 8.06; 95% CI, 3.26-19.93; P < 0.001) and OS (medians not reached, HR, 11.08; 95% CI, 2.16-56.95; P = 0.004). These results were independently associated in multivariate analysis including cfDNA and CTCs for all described endpoints. AR gain patients were less likely to have a ≥50% decline in PSA (OR, 4.93; 95% CI, 1.30-18.75; P = 0.025). Conclusions: Detection of AR gain in plasma using a robust multiplex ddPCR method predicts an adverse outcome in chemotherapy-naïve mCRPC. Further prospective randomized studies are warranted. Clinical trial information: NCT02288936.

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.

AN INDIAN PROSPECTIVE STUDY OF DOCETAXEL THERAPY IN CRPC: CAN PRETREATMENT FACTORS PREDICT THE RESPONSE

2021 ◽  
pp. 78-81
Author(s):  
Devashish Kaushal ◽  
Rajeev Sood
Keyword(s):  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Carcinoma Prostate

Introduction: Studies on the effects of chemotherapy in Indian Castration-Resistant Prostate Cancer (CRPC) patients are very limited and world data is inconsistent. The purpose of the present study is to assess the effects of Docetaxel therapy in CRPC in Indian patients in terms of survival benet, both progression-free survival, and overall survival. This study also analyzes the effects of various factors on the survival of CRPC patients. Methodology: This is a single institutional prospective observational study. CRPC patients were treated with Docetaxel and followed till death as the primary endpoint or till the end of the study. Survivals were calculated with the Kaplan Meier method. Factors affecting survival were analyzed with univariate and multivariate analysis by log-rank t-test and Cox proportion hazard regression analysis. Result: Out of enrolled 101 patients, 78 were treated with Docetaxel. A decline in PSA (>50% reduction) was observed in 61.54%. Radiological response of regression noted in 40 % Nuclear Bone Scan and 19.23% CT/MRI by RECIST criteria. Progression-free survival and overall survival with Docetaxel (n=78) were 11.8 and 21 months respectively. Hemoglobin less than 11 gm%, Alkaline phosphatase more than 115 IU/dl, PSAmore than 14 ng/ml, Gleason score more than 7 and duration from diagnosis of carcinoma prostate to CRPC less than 24 months, the number of chemotherapy cycles less than 6 were all found to be signicantly associated with poor overall survival in univariate analysis while only Hemoglobin (P=0.0159) showed an independent association with overall survival in multivariate analysis. Conclusion: Overall and progression-free survival of CRPC patients with Docetaxel is 21 & 11.8 months respectively. Hemoglobin, Alkaline phosphatase, PSA, Gleason score, Docetaxel cycle, and duration from diagnosis of carcinoma prostate to CRPC were found to be signicantly associated with poor overall survival.

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma, primary tumors, and sites of metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16231-e16231
Author(s):  
Veronica Placencio-Hickok ◽  
Marie Lauzon ◽  
Natalie Moshayedi ◽  
Michelle Guan ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Regression Model ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
High Status ◽  
Free Survival ◽  
Pdac Tissue ◽  
Treatment Naïve

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and < 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

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.

Association Between Second Progression-free Survival (PFS2) and Overall Survival in Metastatic Castration-resistant Prostate Cancer

2020 ◽  
Vol 77 (6) ◽  
pp. 763-766 ◽  
Author(s):  
David Lorente ◽  
Elena Castro ◽  
Rebeca Lozano ◽  
Javier Puente ◽  
Nuria Romero-Laorden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant
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