Clinical utility of CLIA-grade AR-V7 testing in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 183-183 ◽  
Author(s):  
Mark Christopher Markowski ◽  
John Silberstein ◽  
James R. Eshleman ◽  
Jun Luo ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Targeted Therapies ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Line Therapy ◽  
Improved Outcomes ◽  
Practice Methods

183 Background: The AR-V7 splice variant may confer resistance to AR-targeted therapies but not taxane chemotherapies. Since August 2015, a clinical-grade assay to detect AR-V7 mRNA expression in circulating tumors cells (CTC) has been available through a CLIA-certified lab at Johns Hopkins. In the first 12 months after launch, 195 AR-V7 tests were ordered for clinical purposes. We contacted the ordering providers of the first 100 tests using a questionnaire-based survey to determine how (and if) the results of AR-V7 testing were used in clinical practice. Methods: We identified 100 consecutive mCRPC pts who underwent AR-V7 testing in our CLIA lab. Ordering providers received a questionnaire for each test ordered, asking how (and if) the results of the assay affected their clinical decision-making, and whether a PSA50 response was obtained on next-line therapy after AR-V7 testing was performed. Results: 80 of 100 questionnaires were completed by 26 providers from 17 sites across 14 states. AR-V7 assay results were reported either as CTC negative (21/80: 26%), CTC+ AR-V7 negative (26/80: 33%), or CTC+ AR-V7 positive (33/80: 41%). Prevalence of AR-V7 detection increased with prior exposure to AR targeted drugs (Abi/Enza-naive 29%, post-Abi or Enza 39%, post-Abi and Enza 62%). Overall, management was impacted by AR-V7 testing in 54% of cases (43/80), and even more so with AR-V7+ results (see Table). AR-V7+ pts were commonly switched from AR targeted therapies to a taxane (10/19: 53%) or were offered a clinical trial (8/19: 42%). Pts who had a change in management based on AR-V7 testing were more likely to achieve a PSA50 response on next-line therapy than those not changing treatment (18/36: 50% vs 10/30: 33%). Conclusions: Providers used AR-V7 testing to influence clinical practice more often than not. AR-V7+ pts were most often treated with taxane-based therapy or offered a clinical trial, which may have improved outcomes. Clinical qualification of AR-V7 is ongoing. [Table: see text]

scholarly journals Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer

2017 ◽  
pp. 1-9 ◽  
Author(s):  
Mark C. Markowski ◽  
John L. Silberstein ◽  
James R. Eshleman ◽  
Mario A. Eisenberger ◽  
Jun Luo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Messenger Rna ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Specific Antigen ◽  
Clinical Decision ◽  
The United States ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments–certified laboratory at Johns Hopkins University. Methods We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice. Results In all, 142 (95%) of 150 questionnaires were completed by 38 providers from 29 sites across the United States and Canada. AR-V7 test results were reported either as CTC– (28%), CTC+/AR-V7– (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with prior exposure to ATTs (abiraterone and enzalutamide naïve, 22%; after abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%). Overall, management was affected by AR-V7 testing in 53% of the patients and even more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%); management remained unchanged in only 14% of these patients. Overall, patients who had a change in management on the basis of AR-V7 testing were significantly more likely to achieve a physician-reported 50% decline in prostate-specific antigen response on next-line therapy than those who did not change treatment (54% v 31%; P = .015). Conclusion Providers used AR-V7 testing to influence clinical decision making more often than not. Physicians reported that men with AR-V7+ results had the most treatment changes, and such men were preferentially managed with taxane therapy or offered a clinical trial, which may have improved outcomes.

State-of-the-Art Management for the Patient with Castration-Resistant Prostate Cancer in 2012

2012 ◽  
pp. 289-291 ◽  
Author(s):  
Oliver Sartor
Keyword(s):  
Prostate Cancer ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Molecular Stratification ◽  
Castration Resistant ◽  
Radium 223 ◽  
Phase Iii Trials

Overview: Much progress has been made in metastatic castration-resistant prostate cancer (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T, cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new agents, radium-223 and MDV-3100, have recently reported large phase III trials prolonging overall survival and will be submitted for regulatory approval in 2012. One can now begin to ask, is there an optimal sequence for therapies in metastatic CRPC? Despite the recent progress, there is much we do not know and virtually no information on this important question. We know that abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a patient after receiving docetaxel, but we do not know what, if anything, represents the optimal sequence for abiraterone and cabazitaxel. In fact we do not understand how one therapy may affect the response to a subsequent therapy. We are also aware that the pre- and postdocetaxel spaces represent regulatory rather than biologic divisions. In addition, despite the proven role of docetaxel/prednisone, many patients with CRPC are not considered to be suitable for chemotherapy, and worldwide many never receive any form of chemotherapy. What is the optimal management for these patients? Taken together it is reasonable to assess patient preferences, prior therapies and response/tolerance to prior therapies, burden of disease, comorbidities, current symptoms, drug toxicities, out-of-pocket costs, etc., in clinical decision making. Given the many factors we do not know, it is hard to be dogmatic in approaching the therapeutic options for the patient with CRPC. We will likely soon move beyond the current sequencing paradigm and begin to assess new combinations in a systematic and rational fashion. Perhaps one day, in the not too distant future, we will develop molecular “stratification systems” to better guide therapeutic choices in CRPC.

Use of plasma androgen receptor (AR) testing to optimize docetaxel chemotherapy in castration-resistant prostate cancer (CRPC): A multicenter biomarker study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5546-5546
Author(s):  
Vincenza Conteduca ◽  
Elena Castro ◽  
Daniel Wetterskog ◽  
Emanuela Scarpi ◽  
Nuria Romero-Laorden ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Decision ◽  
Digital Pcr ◽  
Castration Resistant Prostate Cancer ◽  
Standard Regimen ◽  
Internal Validation ◽  
Castration Resistant ◽  
Potential Biomarker ◽  
Prospective Trials ◽  
Physician Patient

5546 Background: Plasma AR status has been identified as a potential biomarker of response in CRPC patients receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR in the overall management of CRPC patients (pts) receiving docetaxel at different dose due to the toxicity profiles and physician-patient preferences is unknown. Methods: This was a multi-institution study of associations between baseline plasma AR-copy-number status assessed by droplet digital PCR and outcome in 325 CRPC pts. Between September 2011 and July 2019 pts started treatment with docetaxel administered at standard regimen 75mg/m2 every three weeks or adapted regimen (75-80% of standard recommended dose or 30mg/m2 weekly administration) at the discretion of the treating physician. Patients were assigned randomly into 2 sets with a ratio 2:1 to either training (n=217) and internal validation (n=108) cohorts. Results: In our study, adapted regimen of docetaxel was administered in 68 (31.3%) and 35 (32.4%) of training and validation cohorts, respectively. Based on plasma AR status, 67 (30.9%) and 39 (36.1%) validation and training set pts were classified as AR gain, respectively. In men treated with standard docetaxel regimen, no difference in progression-free/overall survival (PFS/OS) was seen between plasma AR normal and gain in both cohorts. In patients treated with adapted docetaxel regimen, we observed a significantly shorter median PFS (3.9 vs. 6.4 months, HR 4.77, 95%CI 1.48-3.80, p=0.0003) and median OS (11.2 vs . 20.4 months, HR 2.87, 95%CI 1.73-2.13, p=0.0008) in the training cohort. This finding was confirmed in the validation cohort (median PFS: 4.8 vs. 7.4 months, HR 2.54, 95%CI 1.40-4.58, p=0.005, and median OS: 11.8 vs. 26.4 months, HR 5.00, 95%CI 2.59-9.65, p<0.0001). In addition, AR-gained patients were less likely than AR normal to have a PSA decline when receiving an adapted regimen in both cohorts (p=0.010 e p=0.003, respectively). Conclusions: This study suggests that plasma AR may improve clinical decision making in choosing not only between AR-directed therapies and taxanes, but also between adapted and standard regimen of docetaxel in first- and subsequent-therapy lines, providing promising clinical implications to select the proper timing and dose of docetaxel. Prospective trials to validate these findings are warranted.

Clinical outcomes of abiraterone acetate + prednisone (AA) + bone resorption inhibitors (BRI) versus AA alone as first-line therapy for castration-resistant prostate cancer (CRPC) with bone metastases (BM) in an international multicenter database.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 30-30
Author(s):  
Edoardo Francini ◽  
Francesco Montagnani ◽  
Pier Vitale Nuzzo ◽  
Miguel Gonzalez-Velez ◽  
Nimira S. Alimohamed ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Local Therapy ◽  
High Volume ◽  
Clinical Decision ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Cox Models ◽  
Risk Of Death ◽  
Line Therapy ◽  
The Impact

30 Background: BM in patients (pts) with CRPC are associated with shorter overall survival (OS) and higher costs. BRI zoledronic acid and denosumab are frequently used to prevent skeletal-related events (SRE) in pts with CRPC and BM. AA is the most common 1st line therapy for men with metastatic CRPC. We aimed to assess the impact of BRI on OS and time to first SRE (ttSRE) of pts receiving 1st line treatment AA for CRPC with BM. Methods: A retrospective cohort of pts starting AA as 1st line therapy for CRPC with BM between 2013-2016 was identified through 8 hospitals’ IRB approved registries. Pts were classified by use of concomitant BRI and subgrouped by volume of disease (per E3805 definition) at AA start. Kaplan-Meier method and Cox models were used to assess OS and ttSRE with hazard ratio (HR) estimates (95% CI). Results: Of the 745 pts included (543 deaths), 529 (71.0%) had AA alone and 216 (29.0%) AA+BRI. Median follow-up was 23.5 months. Pts receiving concomitant BRI showed a significantly longer OS and a 35% reduced risk of death compared to AA alone (HR=0.65; 95% CI, 0.54-0.79; P<.0001). The OS benefit with BRI was greater for the subgroup with high volume disease (HV) (HR=0.51; 95% CI, 0.38-0.68; P<.0001). The cohort with AA+BRI had a significantly shorter ttSRE (HR=1.27; 95% CI; 1.0-1.60; P=.0439) and, notably, the risk of first SRE was more than doubled for the subgroup with LV (HR=2.29; 95% CI, 1.57-3.35; P<.0001). On MVA, BRI vs. no BRI, prior local therapy (PLT) vs. no PLT, LV vs. HV, baseline VAS pain ≤3 vs. >5, PS 0 vs. ≥1, and PSA are independently associated with longer OS. Conclusions: The addition of BRI to 1st line AA for CRPC men with BM was associated with improved OS, particularly in HV, and worsened ttSRE, more evident in LV. These data suggest a potentially different impact of concomitant BRI on HV vs. LV, which could affect clinical decision making.[Table: see text]

scholarly journals Molecular Testing in Patients With Castration-Resistant Prostate Cancer and Its Impact on Clinical Decision Making

2017 ◽  
pp. 1-11 ◽  
Author(s):  
Derrick L. Tao ◽  
Shawna Bailey ◽  
Tomasz M. Beer ◽  
Erik Foss ◽  
Brooke Beckett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pten Expression ◽  
Molecular Testing ◽  
Castration Resistant Prostate Cancer ◽  
Molecular Abnormalities ◽  
Castration Resistant ◽  
Guided Therapy

Purpose Metastatic castration-resistant prostate cancer (CRPC) is the lethal form of the disease. Many groups have performed mutational or immunohistochemistry (IHC) testing in metastatic CRPC to identify treatment targets. However, the frequency with which mutational or IHC data have an impact on clinical decision making and the outcomes of molecularly guided therapy in CRPC are largely unknown. We report our institution’s experience with mutational and IHC testing in patients with metastatic CRPC and its impact on clinical decision making and patient outcomes. Methods Between 2012 and 2015, 59 patients with CRPC underwent metastatic tissue biopsies and were genotyped with a 37–cancer gene panel in a Clinical Laboratory Improvement Amendments–certified laboratory. PTEN expression by IHC testing was also measured in 35 of these samples. A retrospective chart review was performed to determine whether the genomic information was acted upon and the outcome of patients whose treatment was guided by molecular testing. Results Forty-six of 59 patients with CRPC (78.0%) had biopsies with adequate tumor for mutational testing. Thirty-one of 46 subjects (67.4%) had mutations identified by sequencing. Of the 35 patients with CRPC whose biopsies were evaluated for PTEN expression by IHC testing, 13 had PTEN loss. Two patients had treatment on the basis of molecular testing, and one of these subjects had greater tumor control with molecularly guided therapy than his immediate prior therapy. Conclusion Targeted sequencing and IHC can identify clinically informative molecular abnormalities in CRPC. Despite this, a small minority of patients in our series underwent therapies guided by mutational or IHC testing. Actionability of abnormalities identified in metastatic CRPC may be improved with access to clinical trials, insurance approval for unapproved uses of existing anticancer drugs, and larger gene sequencing panels that include more frequently mutated genes.

Updated safety result of a large Italian early access program (EAP) with cabazitaxel plus prednisone (CbzP) in metastatic castration-resistant prostate cancer (mCRPC) patients who progressed during or after docetaxel (D) therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15185-e15185
Author(s):  
Sergio Bracarda ◽  
Giuseppe Di Lorenzo ◽  
Donatello Gasparro ◽  
Paolo Marchetti ◽  
Francesco Boccardo ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Daily Clinical Practice ◽  
Castration Resistant Prostate Cancer ◽  
Good Tolerability ◽  
Early Access ◽  
Castration Resistant ◽  
Heavily Pretreated ◽  
Practice Methods ◽  
Ecog Ps ◽  
Access Program

e15185 Background: A significant percentage of mCRPC pts, who have progressed on D therapy, have a long life expectancy and are candidates for additional treatments. In TROPIC trial pts who progressed during or after D had a statistically significant OS advantage and clinical benefit with CbzP in respect to mitoxantrone plus prednisone (MP). Benefits observed in the TROPIC study supported a global EAP, to allow pts with mCRPC to have an early access to CbzP and provide confirmatory data in daily clinical practice Methods: We report the safety results of the first 90 pts entered into EAP and treated with CbzP, out of 232 pts enrolled by 25 Italian centers between Jan and Aug 2011 Results: Pts characteristics were median age 70 years (≥ 75 years 22.2%); ECOG PS 0-1, 97.8%; median N. of previous D cycles 8 (median cumulative D 675mg/m2); 14.1% received 675 ÷ 900 mg and 40.0% ≥ 900 mg of D. Median time from last D dose to first CbzP dose was 5.29 months including any other chemotherapy treatment.At the time of this analysis 50% of pts had received 4 cycles of CbzP. 33 pts discontinued CbzP mainly due to PD (42.4%), AEs (related/not related, 27.3%), investigator’s (3.0 %) / pts decision (18.2%) and others (9.1%). AEs resulting in CbzP discontinuation (10.0%) are mainly fatigue, pyrexia and haematological disorders. A total of 57 pts were still on treatment. In the 33 discontinued pts, CbzP has been delayed in 24.2% while a dose reduction occurred in 21.2% of pts. AEs of any grade were observed in 81/90 pts. Most common G 3/4 AEs were leukopenia (25.6%), neutropenia (48.9%), anaemia (6.7%), diarrhoea (1.1%), asthenia (3.3%) and fatigue (5.6%). One death occurred during the study period in a heavily pretreated pt who received 33 cycles of D Conclusions: This preliminary safety analysis suggests the good tolerability of cabazitaxel, in terms of haematological as well as non-haematological AEs even in heavily pretreated pts according to the previous experience of Italian Centers in theTROPIC trial. This is remarkable because of the increased similarity of the patient’ populations treated in the EAP and daily clinical practice

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