Clinical significance of AR amplification from CF DNA among Japanese castration-resistant prostate cancer patients.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 314-314
Author(s):  
Shinichi Sakamoto ◽  
Keisuke Ando ◽  
Nobushige Takeshita ◽  
Satoshi Yamamoto ◽  
Akira Komiya ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Univariate Analysis ◽  
Independent Prognostic Factor ◽  
Serum Testosterone Level ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Significant Factors

314 Background: We study the prognostic ability of androgen receptor amplification (AR amp) from cf DNA in Japanese castration-resistant prostate cancer (CRPC) patients. Methods: Multiple sets of serums were obtained from 38 castration-resistant prostate cancer patient at Chiba University hospital. Serum cfDNA was purified using a cobas cfDNA Sample Preparation Kit. AR copy number was measured using the QX100 Droplet Digital PCR System. Factors associated with progression-free survival (PFS) and Overall Survival (OS) were statistically studied. Results: The number of patients received Enzalutamide (Enza)/Abiraterone (Abi)/Docetaxel (Doc) were 33/25/11. Regarding PFS, the presence of AR amplification, Bone Scan Index (BSI), PSA was significant factors on univariate analysis. On multivariate analysis, AR amplification was an independent prognostic factor (HR. 8.9, p=0.003). Regarding OS, PSA and AR amp was significant factors. On multivariate analysis, AR amp (HR 4.2, p=0.028) was an independent prognostic factor. AR amp was related to the young age, high bone metastasis, high PSA, while no association was identified related the visceral metastasis. Overall, the presence of AR amp was negatively related to the initial ADT periods (r=-0.28). In contrary, among primary resistance cases (initial treatment periods <1 year), AR amp positively related to the treatment periods (r=0.31). Higher nadir testosterone (>15 ng/dL) was related to the higher AR amp (p=0.0169). AR amp was related to the treatment resistance in Enza (p=0.0216), while no relation was observed in Abi or Doc. Conclusions: AR amp significantly correlated with the poor prognosis. Higher serum testosterone level may predict the presence of AR amp in cf DNA. [Table: see text]

Activity of cabazitaxel following docetaxel and abiraterone acetate in patients with castration-resistant prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 186-186 ◽  
Author(s):  
Avishay Sella ◽  
Tal Sella ◽  
Avivit Peer ◽  
Raanan Berger ◽  
Stephen Jay Frank ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Infectious Complications ◽  
Abiraterone Acetate ◽  
Sensitive Period ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients

186 Background: Cabazitaxel (CAB) and abiraterone-acetate (AA) have been approved after docetaxel in castration resistant prostate cancer (CRPC). Both exhibit hormonal effects. AA depletes androgen in microenvironment; taxanes affect the microtubule-dependent trafficking of the androgen receptor. Recently, clinical cross-resistance has been suggested between AA and taxanes. This prompted evaluation of CAB following docetaxel and AA in CRPC. Methods: Over 13 months until December 2011, 130 CRPC patients received AA after docetaxel in compassionate programs. Of them, 24 (18.4%) subsequently received CAB. We retrospectively reviewed their data (PCWG2/RECIST and NCI toxicity criteria). Results: Fourteen (58.3%) received CAB/prednisone at 20 mg/m2 and 10 patients 25 mg/m2, overall a median of 4 (1-13) cycles. Nineteen (79.1%) received primary G-CSF support. Patient characteristics (median, range in parenthesis): Age 65 (57-85) years, Gleason- 8 (6-10), K.S- 80 (50-90) %. Metastatic sites: liver- 5 (20.8%), visceral- 8 (33.3%), osseous- 22 (91.6%), No. sites involved- 2 (1-4). Lab-work: PSA- 128.1 (0.01-1700) ng/ml, PSA Doubling time- 2.16 (0.64-7.41) months, alkaline phosphatase 129 (35-1200) u/L. Castration sensitive period - 16.2 (2.0-92.1) months. Using Cox univariate analysis, only K.S was near-significant for prediction of survival after initiating CAB, p=0.075, OR=0.315, 95% C.I (0.88-1.125). A PSA response of 30%, 95% C.I (11,8-54,2)% was observed after CAB with non progression occurring in 6 (26%) out of 23 evaluable patients, 95% CI (10.2-48.4)%. At analysis 11 patients are alive. Median survival from initiation of CAB was 8.2 (95% C.I 3.34-13.05) months, from AA 16.1 (95 C.I 11.56-20.64) and from docetaxel 32.0 (95% C.I 11.56-39.69). Non-progression with docetaxel (but not AA) was associated with longer survival with CAB, p=0.049, 43.1 v.s 17.4 months. Four (16.6%) patients developed infectious complications, including one death due to septic shock. Conclusions: Limited number of patients with CRPC received CAB following docetaxel and AA. In this selected population CAB was active. Response to prior docetaxel was associated with prolonged survival to CAB therapy.

The effect of corticosteroid (Cs) use during docetaxel (D) treatment on overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16522-e16522
Author(s):  
Fruzsina Gyergyay ◽  
Barna Budai ◽  
Krisztina Biro ◽  
Zsofia Kuronya ◽  
Krisztian Nagyivanyi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Gleason Score ◽  
Cox Regression ◽  
Negative Influence ◽  
Abiraterone Acetate ◽  
Independent Prognostic Factor ◽  
Castration Resistant Prostate Cancer ◽  
Kaplan Meier

e16522 Background: Cs are commonly used in the treatment of mCRPC, because of their inhibitory effects on the secretion of ACTH and their palliative effects. Inhibition of ACTH results in downregulation of adrenal androgens. Cs may have a cytotoxic effect on prostate cancer cells, mediated in part by the downregulation of androgen receptors and the activation of glucocorticoid receptor-mediated signaling and downstream antiangiogenic activity. The rationale for adding Cs to D chemotherapy is for the management of symptoms and adverse events rather than for improving responses. D (without Cs) + ADT (androgen-deprivation therapy) vs ADT alone in castration-sensitive prostate cancer has resulted in significant increase in survival (NEJM, 2015). Cs has been reported to adversely influence OS during enzalutamide (NEJM, 2012). In the COU-AA-301 trial Cs use at baseline was an independent prognostic factor in multivariate analysis, but not in a stepwise selection model (JCO, 2013). Methods: We performed a retrospective analysis of 117 mCRPC pts treated with D. All pts had standard Cs premedication before D and 74 pts received prednisone 5 mg po BID, but 43 pts didn’t get continuous Cs therapy. Kaplan-Meier estimates and Cox regression model were used. Results: Pts characteristics were as follows: median age 66 yrs (range 48-81), Gleason score ≤6: 22pts, ≥7: 61pts. (34 NA). Altogether 1015 cycles of D were given, median 8 (range 2-27). Subsequent therapies were as follows: Abiraterone Acetate (AA) (75), Mitoxantrone (46), Xofigo (5), other chemotherapies (7), none (21). Pts receiving Cs had an inferior OS in all subgroups, although none was significant (Table). Only the Gleason score was an independent prognostic factor in multivariate analysis. Conclusions: Our data suggest, that D therapy withouth Cs is at least as effective as the combination. More data is neccesary to support the suspicion of negative influence of Cs on OS. Thus unnecesarry Cs treatment might be ommited. [Table: see text]

Activity of cabazitaxel following docetaxel and abiraterone acetate in patients with castration-resistant prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16023-e16023 ◽  
Author(s):  
Avishay Sella ◽  
Tal Sella ◽  
Avivit Peer ◽  
Raanan Berger ◽  
Stephen Jay Frank ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Infectious Complications ◽  
Abiraterone Acetate ◽  
Sensitive Period ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients

e16023 Background: Cabazitaxel (CAB) and Abiraterone-acetate (AA) have been approved after Docetaxel in castration resistant prostate cancer (CRPC). Both exhibit hormonal effects. AA depletes androgen in microenvironment; taxanes affect the microtubule-dependent trafficking of the androgen receptor. Recently, clinical cross-resistance has been suggested between AA and taxanes. This prompted evaluation of CAB following Docetaxel and AA in CRPC. Methods: Over 13 months until December 2011, 130 CRPC patients received AA after Docetaxel in compassionate programs. Of them, 24 (18.4%) subsequently received CAB. We retrospectively reviewed their data (PCWG2/RECIST and NCI toxicity criteria). Results: Fourteen (58.3%) received CAB/prednisone at 20 mg/m 2 and 10 patients 25 mg/m2 , overall a median of 4 (1-13) cycles. Nineteen (79.1%) received primary G-CSF support. Patient characteristics (median, range in parenthesis): Age 65 (57-85) years, Gleason- 8 (6-10), K.S- 80 (50-90) %. Metastatic sites: liver- 5 (20.8%), visceral- 8 (33.3%), osseous- 22 (91.6%), No. sites involved- 2 (1-4). Lab-work: PSA- 128.1 (0.01-1700) ng/ml, PSA Doubling time- 2.16 (0.64-7.41) months, alkaline phosphatase 129 (35-1200) u/L. Castration sensitive period - 16.2 (2.0-92.1) months. Using Cox univariate analysis, only K.S was near-significant for prediction of survival after initiating CAB, p=0.075, OR=0.315, 95% C.I (0.88-1.125). A PSA response of 30%, 95% C.I (11,8-54,2)% was observed after CAB with non progression occurring in 6 (26%) out of 23 evaluable patients, 95% CI (10.2-48.4)%. At analysis 11 patients are alive. Median survival from initiation of CAB was 8.2 (95% C.I 3.34-13.05) months, from AA 16.1 (95 C.I 11.56-20.64) and from Docetaxel 32.0 (95% C.I 11.56-39.69). Non-progression with Docetaxel (but not AA) was associated with longer survival with CAB, p=0.049, 43.1 v.s 17.4 months. Four (16.6%) patients developed infectious complications, including one death due to septic shock. Conclusions: Limited number of patients with CRPC received CAB following Docetaxel and AA. In this selected population CAB was active. Response to prior Docetaxel was associated with prolonged survival to CAB therapy.

The outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 316-316
Author(s):  
Berna Yildirim ◽  
Onal Cem ◽  
Fatih KOse ◽  
Ezgi Oymak ◽  
Ali Murat Sedef ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factor ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Significant Prognostic Factor ◽  
Castration Resistant Prostate Cancer ◽  
Entire Cohort ◽  
Castration Resistant ◽  
Curative Radiotherapy ◽  
Psa Progression

316 Background: To evaluate the potential benefit of curative radiotherapy (RT) to primary tumor in metastatic castration resistant prostate cancer (mCRPC) patients treated with abiraterone. Methods: The clinical parameters of 106 mCRPC patients treated with abiraterone in the either pre- or post-chemotherapy setting were retrospectively evaluated. All patients had PSA progression or radiographic progression suitable for metastasis according to the RECIST guidelines with or without PSA progression. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after systemic treatment were analyzed. Local RT to primary tumor and pelvic lymphatics was delivered in 44 patients (41%), while 62 patients (59%) did not have RT to primary tumor. Results: Median follow-up times for patients overall and for those who survived were 14.2 months (range, 2.3–54.9 months) and median OS for entire cohort was 21.9 months. The median OS was significantly higher in patients treated with local RT to primary tumor compared to patients without local RT (p = 0.04). Local RT to prostate and pelvic lymphatics significantly diminished local recurrence rate ( p = 0.003). In univariate analysis, a decline in PSA levels ≥50% of baseline was significant prognostic factor for both OS and PFS in entire cohort and in patients receiving prostate RT. In multivariate analysis, PSA response ≥50 of baseline obtained ≥3 weeks after abiraterone therapy is the only significant prognostic factor for better OS and PFS. Additionally, local RT to prostate is nearly significant prognosticator for improved OS. Patients treated with primary RT to prostate had significantly less progression under abiraterone and longer abiraterone period compared to patients without local prostate RT. Conclusions: Local prostate RT significantly improves OS and local control but not PFS, in mCRPC treated with abiraterone. Patients treated with primary RT to prostate had significantly less progression under abiraterone and longer abiraterone period compared to patients without local prostate RT.

scholarly journals Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment

2021 ◽  
Vol 9 (10) ◽  
pp. e002919
Author(s):  
Sumit K Subudhi ◽  
Bilal A Siddiqui ◽  
Ana M Aparicio ◽  
Shalini S Yadav ◽  
Sreyashi Basu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Measurable Disease

BackgroundImmune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone.HypothesisCombined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone.Patients and methodsIn this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline.ResultsTwenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints.ConclusionsTremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment.Trial registration numberNCT03204812.

scholarly journals SEQUENTIAL THERAPY OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: NEW POSSIBILITIES

2018 ◽  
Vol 14 (3) ◽  
pp. 120-127 ◽  
Author(s):  
A. S. Markova ◽  
V. B. Matveev ◽  
B. M. Nazranov
Keyword(s):  
Prostate Cancer ◽  
Sequential Therapy ◽  
Therapeutic Agents ◽  
Continuous Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Standards ◽  
Factors Affecting ◽  
Castration Resistant ◽  
Line Therapy ◽  
Significant Factors

Currently, doctors have at their disposal a number of drugs prolonging life of patients with castration-resistant prostate cancer (CRPC). The majority is approved for use as the 1st line therapy and, in absence of direct comparison, is considered potentially equally effective. Patients with CRPC need continuous treatment for suppression of disease progression resulting in sequential use of therapeutic agents. Modern standards and recommendations do not provide a clear algorithm for prescription, therefore an individual approach is necessary taking in account various factors of a particular case ranging from previous therapies to patients’ preferences. This article considers the most significant factors affecting CRPC therapy selection and ways of therapy optimization in compliance with the established treatment standards and taking into account the list of drugs approved for use in Russia.

scholarly journals Economic Evaluations of Cabazitaxel for Treatment of Post-docetaxel Metastatic Castration-resistant Prostate Cancer: Evidence from a Systematic Review

2019 ◽  
pp. 1-8
Author(s):  
Nikinaz Ashrafi Shahmirzadi ◽  
Pardis Zaboli ◽  
Monireh Afzali ◽  
Bereket Molla Tigabu ◽  
Mirhamed Hajimiri ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Cost Effective ◽  
Bibliographic Databases ◽  
Economic Evaluations ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Number Of Patients ◽  
Effective Option

Background and Objectives: Prostate cancer is an ever-increasing global incidence and has become the fifth leading cause of cancer-related mortality in men. A significant number of patients with prostate cancer develop metastatic castration-resistant prostate cancer (mCRPC). There are a few second-line treatment options for patients with post-docetaxel mCRPC. This systematic review aimed to assess the cost-effectiveness of cabazitaxel for the treatment of mCRPC. Materials and Methods: Electronic bibliographic databases including: PubMed/Medline, NICE, CRD, and Scopus were searched in January 2018 for identifying full economic evaluations published in English and Persian. The risk of assessment bias and descriptive analyses of individual studies’ findings were presented. Results: Three articles that fulfilled the inclusion criteria were included in the current study. All the included records had a reasonable quality. Cabazitaxel was not recommended as the most cost-effective option for the treatment of docetaxel-refractory mCRPC. Abiraterone acetate and radium-223 were the recommended cost-effective treatments for mCRPC treatment. Conclusion: We found that, in general, while cabazitaxel had equal or slightly higher improvement in Quality-adjusted Life Year (QALY) as compared to the alternatives, it incurred a high cost. Despite the inclusion of a few studies in this review, cabazitaxel was not found to be a cost-effective option. Therefore, we recommend full economic evaluations to be conducted in this area.

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