Durable radiologic and clinical disease stability beyond PSA progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4553-4553
Author(s):  
Diletta Bianchini ◽  
Shahneen Kaur Sandhu ◽  
Amy Mulick Cassidy ◽  
Andrea Zivi ◽  
Janusz Mezynski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Clinical Disease ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Ecog Performance Status ◽  
Conversion Rates ◽  
Psa Progression

4553 Background: AA, a potent oral CYP17A1 inhibitor is approved for treatment of mCRPC with a survival advantage of 4.9 months. In clinical practice, response evaluation remains challenging for pts with mCRPC. CTC conversion from CTC ≥ 5 to CTC < 5 with treatment predicts for improved overall survival in mCRPC. We hypothesized that pts continue to have durable disease stability beyond PSA progression on AA. Methods: Prostate Specific Antigen (PSA) responses, radiological responses and CTC conversion rates were retrospectively analysed in pts treated on AA at our institution. CTCs, PSA and imaging were obtained at predefined time points during these studies. Radiological and PSA progression were defined by standard Prostate Cancer Working Group Criteria II. Clinical progression consisted of worsening disease related pain, skeletal events or declining performance status.Pearson’s chi-squared test and the Kaplan-Meier method were used for this analysis. Results: 141 patients [ECOG Performance Status 0-2; Median Age: 69.7 (range 44.7-87.1); 85 post-docetaxel, 56 pre-docetaxel] received AA. The median duration of clinical and radiological stable disease (SD) was 16.8 months (n=55) and 5.6 months (n=75) in patients with a baseline CTCs count of ≤ 5 cells/7.5mls and ≥ 5 cells/7.5 mls respectively. In the 105 patients with documented PSA progression on AA there was a median 5.7-month delay in detecting radiological and/or clinical progression (95% CI: 4.2, 8.4; range 0.3, 35.6 months). Radiological and clinical SD of ≥ 1 year, ≥ 2 years and ≥ 3 years on AA was observed in 43/141 (30.5%), 21/141 (14.9%) and 12/141 (8.5%) respectively. Conclusions: Radiological and clinical disease stabilization beyond PSA progression is maintained in a high proportion of mCRPC patients treated with AA. Future studies should evaluate whether continued AA treatment beyond PSA and radiological progression can impact outcome.

scholarly journals A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration resistant prostate cancer

2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
Study Results

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

Comparison of enzalutamide and bicalutamide in patients with non-metastatic castration-resistant prostate cancer: Number needed to treat to achieve one additional patient free of clinical progression events.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 228-228
Author(s):  
Lawrence Ivan Karsh ◽  
David F. Penson ◽  
Raoul Concepcion ◽  
Scott Flanders ◽  
Bruce A. Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Absolute Risk ◽  
Specific Antigen ◽  
Additional Patient ◽  
Number Needed To Treat ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Free Psa ◽  
Castration Resistant ◽  
Psa Progression

228 Background: Androgen receptor inhibitors enzalutamide (ENZA) and bicalutamide (BIC) are used to treat metastatic castration-resistant prostate cancer (mCRPC). The Phase 2 STRIVE trial included 35% non-metastatic (m0) and 65% metastatic CRPC patients (pts); ENZA reduced the risk of progression or death among pts, with an adverse event profile consistent with previous trials. The objective of this analysis was to compare ENZA with BIC using the number needed to treat (NNT) to achieve one additional pt with m0CRPC, with either a progression-free survival (PFS) event, radiographic PFS (rPFS), or free of prostate-specific antigen (PSA) progression at 1 year and 2 years. Methods: The 1- and 2-year event rates of PFS, rPFS, and progression-free PSA among pts treated with ENZA and BIC were obtained from the STRIVE trial report. The NNT was calculated as the reciprocal of the absolute risk reduction between ENZA and BIC at each time point. This represents the number of pts that need to be treated with ENZA, compared with BIC, to obtain one additional pt free of a clinical progression event. PFS was defined as the time from randomization to investigator-assessed radiographic (bone or soft tissue) progression, PSA progression, or death. The 95% confidence interval (CI) of the NNT was derived based on the 95% CI of the event rate difference. Results: The NNT to achieve one additional pt with PFS at 1 year, comparing ENZA with BIC, was 2.2 (95% CI 1.7, 3.4), suggesting that treating three pts with ENZA instead of BIC would result in one additional pt free of progression or death at the end of 1 year. The NNT to achieve one additional pt with PFS at 2 years was also 2.2 (95% CI 1.5, 3.7). For rPFS, the NNTs comparing ENZA with BIC were 4.7 (95% CI 2.8, 14.6) and 3.0 (95% CI 2.0, 6.1) at 1 and 2 years, respectively. For progression-free PSA, the NNTs were 2.0 (95% CI 1.5, 2.8) and 2.0 (95% CI 1.4, 3.3) at 1 and 2 years, respectively. Conclusions: This analysis supports the superior clinical benefit of ENZA versus BIC in men with m0CRPC. Pts treated with ENZA showed low NNT values across all clinical outcomes and time points. Clinical trial information: NCT01664923.

Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Bo Zhao ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Brian I. Rini ◽  
Robert Dreicer
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Underlying Mechanism ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.

scholarly journals Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer: a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes

2018 ◽  
Vol 10 ◽  
pp. 175883401774581 ◽  
Author(s):  
Alessia Cavo ◽  
Alessandra Rubagotti ◽  
Elisa Zanardi ◽  
Chiara Fabbroni ◽  
Linda Zinoli ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Fluid Retention ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Cardiac Disorders

Background: The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. Methods: This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel). Multivariable Cox proportional hazards models assessed factors associated with progression-free survival (PFS) and overall survival (OS). Results: Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml ( p = 0.007), Gleason Score >7 ( p = 0.008), Eastern Cooperative Oncology Group (ECOG) performance status (PS)1–2 ( p = 0.002), duration of androgen deprivation therapy (ADT) ⩽ 43.2 months ( p = 0.01), and body mass index (BMI) > 25 ( p = 0.03) were associated with worse PFS; presence of pain ( p = 0.01), ECOG PS1–2 ( p = 0.004), duration of ADT ⩽ 43.2 ( p = 0.05), and BMI > 25 ( p = 0.042) were associated with worse OS. Incidence of CVEs was as follows: hypertension 17.1%, fluid retention 4.8%, cardiac disorders 8.6%. 16.2% of patients developed hypokalemia. Age ⩾ 75 years was associated with higher probability of cardiac disorders ( p = 0.001) and fluid retention ( p = 0.03). CVEs did not impact on PFS or OS. Hypokalemia was associated with better median OS ( p = 0.036). Similar associations were observed after stratification by subgroup. Conclusions: Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.

scholarly journals Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (9) ◽  
pp. 1496-1501 ◽  
Author(s):  
Daniel C. Danila ◽  
Michael J. Morris ◽  
Johann S. de Bono ◽  
Charles J. Ryan ◽  
Samuel R. Denmeade ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Circulating Tumor Cell ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant

Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was ≥ 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A ≥ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from ≥ 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

2020 ◽  
pp. 107815522095161
Author(s):  
Özgecan Dülgar ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Seval Ay ◽  
Deniz Tural ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
One Year

Objective Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). Material and Method We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Results Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. Conclusion TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 7-7 ◽  
Author(s):  
Matthew Raymond Smith ◽  
Emmanuel S. Antonarakis ◽  
Charles J. Ryan ◽  
William R. Berry ◽  
Neal Shore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase I ◽  
Phase Ii ◽  
Nuclear Translocation ◽  
Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Psa Response ◽  
Psa Progression

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods: All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Clinical trial information: NCT01171898.

Correlation of a novel whole blood RT-PCR assay measuring AR-V7 expression with outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate (ABI).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 223-223
Author(s):  
Tilman Todenhöfer ◽  
Arun Azad ◽  
Craig Stewart ◽  
Jian Gao ◽  
Bernhard J. Eigl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Blood ◽  
Performance Status ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Ecog Performance Status

223 Background: Expression of androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) has been associated with resistance to ABI and enzalutamide (ENZ) (Antonarakis et al. N Engl J Med 2014). We have developed a RT-PCR assay that is neither time sensitive nor requires CTC enrichment for detection of prostate cancer (PCa)-associated transcripts in whole blood. Using this assay, our aim was to correlate AR-V7 expression with outcomes on ABI. Methods: 2.5 ml whole blood was collected into PAXgene RNA tubes from mCRPC patients (pts) commencing ABI. RT-PCR was performed for the following genes: AR-V7, FOXA1, GRHL2, HOXB13, KLK2, KLK3 and TMPRSS2:ERG. For each gene, the highest CT value among 20 normal controls was set as the threshold for a positive (+) test. Clinical endpoints were PSA50 response rate (RR) (PSA decline ≥ 50% confirmed ≥ 3 weeks later), PSA30 RR, time to PSA (PCWG2 criteria) or clinical progression (change in anti-cancer therapy or decline in ECOG performance status (PS) ≥ 2 levels due to PCa), and overall survival (OS). Results: Whole blood samples were obtained from 37 pts. Median age was 70. 59% received prior docetaxel. All pts were ABI and ENZ naïve. PSA50 RR was 37% and PSA30 RR was 48%. Median progression-free survival (PFS) was 3.8 months (mos) and median OS was 21.0 mos. 11% (4/37) of pts were AR-V7+. AR-V7+ pts were more likely to have high ALP (P= 0.04; Χ2), high LDH (P= 0.07) and ECOG PS ≥ 2 (P= 0.052). Pts with an AR-V7+ test had lower PSA50 RR (0% vs. 42%, P= 0.10; Χ2) and PSA30 RR (0% vs. 52%, P= 0.051) together with shorter median PFS (0.7 mos vs. 4.0 mos, P< 0.001; log-rank) and median OS (5.5 mos vs. 22.1 mos, P< 0.001). Other factors linked with worse OS were high ALP (P= 0.02), liver metastases (P= 0.03), ≤ 36 mos on primary hormone therapy (P= 0.04), HOXB13+ (P= 0.03) and KLK2+ (P< 0.001). Conclusions: RT-PCR detection of AR-V7 transcripts in whole blood was associated with a 0% PSA RR and significantly inferior PFS and OS in pts treated with ABI. These results reinforce the potential utility of AR-V7 as a prognostic and predictive biomarker for mCRPC. Validation of the assay in larger datasets is ongoing.

Serum-based biomarkers and liver metastases in metastatic castration-resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 372-372
Author(s):  
Patrick Cotogno ◽  
Lahiru Ranasinghe ◽  
Elisa Ledet ◽  
Brian E. Lewis ◽  
A. Oliver Sartor
Keyword(s):  
Prostate Cancer ◽  
Liver Metastases ◽  
Performance Status ◽  
Specific Antigen ◽  
Elevated Serum ◽  
Clinical Trial Data ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Mri Imaging ◽  
Ecog Performance Status

372 Background: Metastatic castrate-resistant prostate cancer patients with liver metastases have a poor prognosis. No large studies to date have investigated the clinical and biochemical parameters associated with liver metastases in this population. Methods: Patient data was obtained from 1,281 men with mCRPC that were enrolled on to three phase III clinical trials for the treatment of their disease. This clinical trial data was obtained from Project Data Sphere (www.projectdatasphere.org), an initiative of the CEO Roundtable on Cancer's Life Sciences Consortium. Multiple logistic regression was performed on clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline CT/MRI imaging. Variables assessed included prior docetaxel exposure, ECOG performance status, albumin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), hemoglobin, lactate dehydrogenase (LDH), prostate specific antigen (PSA), and total bilirubin. The investigation included lab variables when treated as both dichotomous (based on normal-abnormal ranges) and continuous. Results: Multiple variable analysis demonstrated that an abnormally elevated serum AST and/or LDH was associated with an increased likelihood of having documented radiographic liver metastases (p < 0.0001). The predicted probability of having liver metastases for an abnormally elevated AST or LDH was 13.90% (95% CI 9.12 – 20.59) and 16.80% (95% CI 13.19 – 21.16), respectively. Patients with both an elevated AST and LDH had a 31.31% (95% CI 24.0 – 39.73) probability of having liver metastases as compared to only 6.67% (95% CI 5.17 – 8.57) for those with normal values. The ROC curve for the final model (AST + LDH) containing dichotomous predictors was 0.6683 (p < 0.0001), which was not significantly different when treating the predictors as continuous (p = 0.4858). Conclusions: Our analysis demonstrated a significant association between the presence of liver metastases and elevated serum levels of AST and LDH. More research is needed to validate these biomarkers and determine their application in the clinical setting.

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