Enzalutamide in men with prostate cancer resistant to docetaxel and abiraterone.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 247-247 ◽  
Author(s):  
Mark Creamer Scholz ◽  
Richard Y. Lam ◽  
Jeffrey S. Turner ◽  
Khang N. Chau ◽  
Lauren K. Becker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stable Disease ◽  
Retrospective Chart Review ◽  
Early Access ◽  
Fda Approval ◽  
Heavily Pretreated ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant

247 Background: Since FDA approval in 2011, abiraterone (Zytiga) has supplanted docetaxel as preferred first-line treatment for metastatic castrate-resistant prostate cancer. In August 2012 enzalutamide (Xtandi) was FDA-approved for the treatment of castrate-resistant prostate cancer after docetaxel (Taxotere). We performed a retrospective chart review at a large medical oncology clinic specializing in prostate cancer to determine the PSA response rates of enzalutamide administered to men who had previously progressed on both abiraterone and docetaxel. This report includes some patients who participated in the Astellas/Medivation-sponsored Early Access Program; however, it represents the author’s independent clinical experience. Methods: Enzalutamide was administered at a dose of 160 mg daily. Patients were subsequently followed with monthly physical examination, PSA and routine blood tests. No hepatotoxicity or seizures occurred. Men were considered evaluable for PSA response if they received enzalutamide for twelve weeks. A PSA decline of 30% from baseline after 12 weeks was defined as a response. A PSA increase of 30% from baseline within 12 weeks was defined as disease progression. Men with neither a 30% increase nor a 30% decline were classified as having stable disease. Results: 66 men were treated and 63 were evaluable for PSA response. Median age was 67. Median baseline PSA was 68.5. All participants had disease that had progressed on abiraterone. 55 men received previous docetaxel. 38 had received previous Provenge. Two men stopped before 12 weeks because of intolerable fatigue. One man died of progressive disease before 12 weeks. After a median follow up of 12.5 weeks, 18(29%) men met criteria for PSA response. 13(21%) men had stable disease and 32(51%) men had PSA progression. Conclusions: Enzalutamide has activity in a heavily pretreated population of men resistant to abiraterone and docetaxel.

scholarly journals Exceptional Response to Everolimus in a Patient with Metastatic Castrate-Resistant Prostate Cancer Harboring a PTEN Inactivating Mutation

2020 ◽  
Vol 13 (1) ◽  
pp. 456-461 ◽  
Author(s):  
Jamie A. Kmak ◽  
Nikita Agarwal ◽  
Yuting He ◽  
Andreas M. Heilmann ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Stable Disease ◽  
Medical Intervention ◽  
Genomic Profiling ◽  
Heavily Pretreated ◽  
Comprehensive Genomic Profiling ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Inactivating Mutation

Prostate cancer is among the most common types of cancer in men. Early detection and proper medical intervention is crucial to ensuring successful treatment. Here we describe a patient clinically presenting with castrate-resistant prostate carcinoma. Comprehensive genomic profiling identified a PTEN inactivating mutation in the patient’s tumor. After being heavily pretreated, the patient showed stable disease on everolimus, a PI3K-Akt-mTOR pathway inhibitor.

Prevalence of ARV7 in Asian metastatic castrate-resistant prostate cancer (mCRPC) patients using multiple detection platforms.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 245-245
Author(s):  
Johan Chan ◽  
Whee Sze Ong ◽  
Quan Sing Ng ◽  
Chee-Keong Toh ◽  
Tanujaa Rajasekaran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lower Risk ◽  
Progression Free Survival ◽  
Detection Methods ◽  
Free Survival ◽  
Blood Samples ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant

245 Background: The presence of AR-V7 in metastatic castrate resistant prostate cancer (mCRPC) men has been associated with worse outcome in men initiated on 2nd generation androgen receptor signalling inhibitors (ARSI) in the Caucasian population. A multinational study was conducted to investigate this in the Asian population. Methods: mCRPC patients were recruited prospectively across 5 countries. Blood samples were collected and processed from patients with progressive disease immediately before the initiation of a new treatment and at progression. AR-V7 detection were performed using 3 methods: CTC enrichment followed by automated immunofluorescent staining (Clearbridge [CB]), CTC enrichment followed by reverse-transcription PCR analysis (IBN), and the AdnaTest Prostate Cancer(Adna) platform for CTC analysis and detection. Only blood samples collected in Singapore underwent all 3 methods of detecting AR-V7. Comparison of AR-V7 prevalence using the 3 detection methods were done on patients with the AdnaTest platform as gold standard. We examined associations between AR-V7 status and PSA response rates, PSA progression free survival and overall survival(OS). Results: 102 patients were recruited. 72 patients had ARSi while 30 patients had chemotherapy. 66 patients were included for the comparison of AR-V7 detection methods. AR-V7 prevalence rate was 14.3% (95% CI 4.8-30.3), 21.6% (95% CI 12.9-32.7) and 33.7% (95% CI 24.6-43.8) based on Adna, CB and IBN respectively. Concordance between Adna and CB was 75% while Adna and IBN was 68%. AR-V7- patients had a trend towards higher PSA response, lower risk of PSA progression as compared to AR-V7+ patients. AR-V7- patients had a significantly lower risk of death as compared to AR-V7+ patients detected by Adna and IBN platforms but not the CB platform. The association between ARV7 status and outcomes did not vary when compared across treatment groups. Conclusions: AR-V7 positivity in Asian mCRPC patients is consistent with the data reported in Western populations with lower PSA response rates, PSA progression free survival and OS. This data suggest that ARV7 is more likely a prognostic than a predictive biomarker. Clinical trial information: 2015/2797.

A phase II study to evaluate the effects of docetaxel plus lycopene in advanced castrate-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 77-77
Author(s):  
Eric Zhuang ◽  
Edward M. Uchio ◽  
Michael B. Lilly ◽  
John P. Fruehauf
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Median Time ◽  
Response Rate ◽  
Phase Ii Study ◽  
Duration Of Response ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant

77 Background: Lycopene, the carotenoid responsible for the red colors seen in tomatoes, grapefruit, and other foods, has demonstrated synergism with docetaxel in prostate cancer cell culture and tumor xenograft models. This phase II study investigated the clinical activity and safety profile of docetaxel plus lycopene in advanced castrate resistant prostate cancer. Methods: Eligible patients had histologically confirmed adenocarcinoma of the prostate, two rising pre-study prostate specific antigen (PSA) values ≥ 1 ng/ml, and no prior treatment with any chemotherapy, biological therapy, or investigational drug. All patients initially received docetaxel 75mg/m2 every 21 days in combination with lycopene 30 mg orally once daily. The primary endpoint was PSA response rate, defined as the proportion of subjects achieving a ≥ 50% reduction in PSA at any point after starting therapy. Secondary endpoints included median time to PSA progression, duration of response (DOR), and overall survival (OS). Results: Fourteen patients were screened, and thirteen patients were initiated on protocol therapy. Median age was 77 years (range 55-90). Twelve patients (92%) had bone metastases. Four patients (30%) had bone and visceral metastases. The PSA response rate was 76.9% [95% confidence interval (CI), 46.2-94.9], comprising of ten PSA responses. Two patients had a best response of stable disease, yielding a disease control rate of 92% [95% CI, 57.2-98.2]. Median time to PSA progression was 8 months [95% CI, 3.5-8.7]. Median duration of response was 7.3 months [95% CI, 4.8-13.2]. On 5-year follow-up, median overall survival was 35.1 months [95% CI, 25.7-57.7]. The most frequently reported ( > 15%) non-hematologic adverse events included diarrhea, nausea, vomiting, peripheral neuropathy, weight loss, fatigue, onycholysis, and alopecia. One patient (7%) experienced febrile neutropenia. No patients experienced grade 3 or above anemia. Conclusions: The combination of docetaxel with lycopene led to improved PSA response rate and tolerability in patients with advanced castrate resistant prostate cancer. Docetaxel plus lycopene merits further research in this patient population. Clinical trial information: NCT01882985.

Enzalutamide after abiraterone in patients with metastatic castrate-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 240-240 ◽  
Author(s):  
Gurprataap Singh Sandhu ◽  
Rahul Atul Parikh ◽  
Leonard Joseph Appleman ◽  
David Friedland
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Single Center ◽  
Androgen Receptor Signaling ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant ◽  
Docetaxel Chemotherapy ◽  
Modest Activity

240 Background: Abiraterone is a 17a hydroxylase and C17,20-lyase inhibitor that blocks androgen biosynthesis and is approved for treatment in patients with mCRPC. Enzalutamide, a second-generation androgen receptor signaling inhibitor was recently approved for use in patients with mCRPC post-docetaxel. There is paucity of information regarding sequential use of enzalutamide after abiraterone. Methods: This is a single-center, retrospective analysis of 23 patients with mCRPC who received enzalutamide after progression on abiraterone. Post-treatment prostate specific antigen(PSA) response and time to PSA progression were used to determine enzalutamide efficacy. Patients were followed for 6 months post initiation of enzalutamide. Results: At the time of enzalutamide initiation, median age was 70 years, with average Gleason score of 7 at the time of diagnosis. All patients were on ongoing androgen deprivation therapy, and 15 patients had received prior docetaxel chemotherapy. Median duration of abiraterone and enzalutamide treatment was 7 and 4.5 months respectively. 12 patients had at least one declining PSA value post enzalutamide treatment, with 5 patients showing >25% decline in PSA and 4 patients > 50%. Median time to PSA progression in patients receiving enzalutamide following abiraterone was 2.3 months. Conclusions: Sequential enzalutamide in patients with CRPC post-abiraterone showed only modest activity, indicating that the clinical benefit of sequential use of highly potent androgen pathway inhibitors cannot be assumed, and should be measured in prospective studies.

βIII-tubulin expression as a predictor of docetaxel resistance in metastatic castrate-resistant prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15174-e15174
Author(s):  
Bertha E. Sanchez ◽  
Nilesh Gupta ◽  
Meredith Mahan ◽  
Evelyn R Barrack ◽  
Prem-veer Reddy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Clinical Decision Making ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Docetaxel Resistance ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
The Mean ◽  
Castrate Resistant

e15174 Background: Docetaxel is a tubulin-targeting cytotoxic that remains first-line therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) even though half of pts are reported to be non-responders. A predictive marker to identify those who will benefit from docetaxel-therapy will assist clinical decision making. High βIII-tubulin (TUBB3) expression has previously been reported to correlate with lack of response to taxanes in other cancers. We evaluated TUBB3 expression as a predictor of docetaxel-resistance in mCRPC. Methods: mCRPC pts treated with at least 3 cycles of docetaxel between 1990 and 2011 were identified retrospectively. TUBB3 immunostaining was performed on archival formalin-fixed, paraffin-embedded tissue. Stain intensity was scored from 0 to 3; 2 and 3 were interpreted as positive. Rates of PSA response were compared between pts with positive (+) and negative (-) TUBB3 expression. Two definitions of PSA response were evaluated (any PSA decline and at least 50% decline). Overall survival (OS) distribution between TUBB3+ and TUBB3- pts was estimated by the Kaplan-Meier method. Results: Of 73 pts, 26 (35%) expressed TUBB3. At diagnosis, the mean age was 65.7 years and the median Gleason score was 8. At the time of docetaxel therapy, the mean age was 71.2 years, the median PSA level was 70.9 (range, 0.2-5253) and 76% had ECOG performance status ≤1. The median number of docetaxel cycles was 7 (range, 3-18). The total dose of docetaxel was not different between groups (p=0.705). The median OS was 19.2 mo. TUBB3 expression was not correlated with any clinical or pathological characteristic (age, Gleason score, stage, ECOG, PSA, LDH, alkaline phosphatase, hemoglobin, visceral disease or chemotherapy before docetaxel). 65% of TUBB3+ pts had any PSA decline compared to 89% of pts with TUBB3- (p=0.0267). 52% of TUBB3+ pts had a PSA decline of ≥ 50% compared to 70% of TUBB3- pts (p=0.0144). Median OS for TUBB3+ pts was 16.8 mo compared to 20.4 mo in TUBB3- pts (p=0.039). Conclusions: High TUBB3 expression was associated with shorter OS and lower PSA response rates in mCRPC pts treated with docetaxel. These findings need to be validated prospectively.

Trends in utilization of novel oral therapeutic agents for men with metastatic castrate-resistant prostate cancer within the United States Veteran’s Affairs Health System.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 220-220
Author(s):  
Elizabeth Henry ◽  
Abigail Silva ◽  
Elizabeth Tarlov ◽  
Ellen R. Gaynor
Keyword(s):  
Prostate Cancer ◽  
The United States ◽  
Treatment Patterns ◽  
Prescribing Patterns ◽  
First Line ◽  
Androgen Synthesis ◽  
Fda Approval ◽  
Oral Agents ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

220 Background: Therapeutic options for men with metastatic castrate resistant prostate cancer (mCRPC) have expanded significantly over the past 5 years with several new agents demonstrating improved survival, including two oral agents. Abiraterone acetate (AA), a CYP-17 androgen synthesis inhibitor, obtained initial FDA approval in 2011 for post-docetaxel (D) use, and gained expanded approval in 2012 for pre-D use. Enzalutamide (ENZ), an androgen receptor signaling inhibitor, also gained FDA approval in 2012 (post-D) and indication was expanded in 2014 (pre-D). Due to the relatively recent approvals of these agents, there is limited data on rates of uptake and prescribing patterns for patients (pts) with mCRPC. Methods: For this observational study, Veterans Affairs (VA) healthcare system data (including hospitalizations, outpatient visits, and pharmacy) were used to identify male veterans who received treatment for mCRPC between fiscal years 2008 and 2014. Descriptive statistics were used to classify treatment patterns. Results: During the time period, 75,199 pts with prostate cancer were medically or surgically castrated. Of those, 43,805 were treated with anti-androgens and 7,890 went on to receive advanced lines of therapy associated with mCRPC. The median age at the time of mCRPC treatment was 73y. Between 2008-2010 (pre-AA) and 2011-2014 (post-AA), the proportion of mCRPC pts treated with ketoconazole or D dropped from 95% to 59% (p < 0.0001). Conversely, the proportion of pts who received AA or ENZ increased from 19% to 68% (p < 0.0001). Among the 3,763 pts treated with AA or ENZ between 2011 and 2014, the proportion treated with first-line D decreased, while the proportion treated with first-line AA increased (p < 0.00001). Conclusions: The FDA approval of AA and ENZ has had a significant impact on treatment patterns for men with mCRPC within VA, with decreased use of ketoconazole and delayed use of chemotherapy. Further information regarding patient and disease characteristics is needed. The rapid uptake of these novel agents has significant implications for disease-related outcomes as well as anticipated pharmacy costs within the VA.

Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)-pretreated patients (pts) with metastatic castrate resistant prostate cancer (mCRPC): Cohort B of the phase 1b/2 KEYNOTE-365 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Christophe Massard ◽  
Margitta Retz ◽  
Peter Hammerer ◽  
Fernando Quevedo ◽  
Peter C.C. Fong ◽  
...  
Keyword(s):  
End Points ◽  
Immune Mediated ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Pretreated Patients ◽  
Phase 1B ◽  
Grade 3 ◽  
Castrate Resistant

5029 Background: Pembro had activity as monotherapy in pretreated advanced mCRPC. Data are presented here from cohort B (pembro + docetaxel/prednisone) of KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study to test combinations in mCRPC. Methods: Pts who progressed on or became intolerant to ≥4 wk of abi or enza in the prechemotherapy mCRPC state and progressed within 6 mo before screening were eligible. Pts received pembro 200 mg IV with docetaxel 75 mg/m2 IV Q3W plus prednisone 5 mg orally twice daily. The primary end points were safety and PSA response rate (confirmed PSA decrease ≥50%). Key secondary end points were investigator-determined ORR (RECIST v1.1), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, rPFS, and OS. Results: 72 pts (median age, 68 y; visceral disease, 36%; measurable disease, 50%) began pembro + docetaxel. Median (95% CI) follow-up was 10 (8-12) mo. Efficacy is outlined in the table. Treatment-related AEs occurred in 69 (96%) pts; most frequent (≥30%) were alopecia (43%), fatigue (40%), and diarrhea (39%). Grade 3-5 treatment-related AEs occurred in 27 (38%) pts, including 2 deaths from treatment-related AEs (pneumonitis). Most commonly reported immune-mediated AEs were infusion-related reactions (11%) and colitis (10%). Conclusions: Pembro + docetaxel/prednisone has activity in pts with mCRPC who previously progressed on second-generation hormone therapy. AEs were considered mild for the treatment combination. Clinical trial information: NCT02861573. [Table: see text]

The use of intermittent enzalutamide dosing in the treatment of metastatic castrate-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 81-81
Author(s):  
Michael Rowe ◽  
Ayesha Hidayat ◽  
Stuart Walter ◽  
Adam Pollard ◽  
Timothy Norris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Time ◽  
Median Number ◽  
Significance Level ◽  
Kaplan Meier ◽  
Single Centre Study ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Continuous Scheduling

81 Background: Intermittent hormone manipulation in castrate-sensitive prostate cancer can improve quality of life whilst maintaining comparable disease outcomes with continuous scheduling. Enzalutamide is effective in metastatic castrate-resistant prostate cancer (mCRPC) treatment but can have significant side-effects. We conducted a retrospective analysis of patients treated with intermittent enzalutamide compared with continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC at Royal Cornwall Hospital from September 2011 to February 2018 were included. Data was collected from electronic medical records, selecting patients with at least a 1 month treatment break. Kaplan-Meier analysis of overall survival from enzalutamide start (OS), time to PSA failure (TTF) and total enzalutamide treatment time (TTT) was calculated for intermittent and continuous responders (>50% PSA drop), assigned significance level of 0.05. Results: 243 patients received enzalutamide, 110 (45%) were continuous responders and 29 (12%) had intermittent dosing. All patients treated intermittently had a PSA response prior to first treatment break, which was most commonly for fatigue (60%). 25% were still receiving enzalutamide. Median number of breaks was 1 (range 1-7), time on treatment was 70% and time to first break was 5 months. The intermittent group had significantly improved OS with median not reached, median OS for continuous responders was 19 months (HR 2.39, 95% CI 1.53-3.76, p=0.002). The intermittent group had prolonged TTF (median 13 vs 6 months, p=0.001) and TTT (median 30 vs 10 months, p=0.0003). Conclusions: Intermittent dosing of enzalutamide in these mCRPC patients does not adversely impact OS, increasing time patients remain on treatment. However, this was a small, retrospective, single-centre study; prospective trials are necessary to clarify the role of intermittent enzalutamide.[Table: see text]

Development of a predictive model of PSA response to a switch from prednisone to dexamethasone in metastatic castrate-resistant prostate cancer patients biochemically progressing on abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 88-88
Author(s):  
Reeta Barua ◽  
Cameron Phillips ◽  
Vanessa Sarah Arciero ◽  
Liying Zhang ◽  
Amanda Rahmadian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Performance Status ◽  
Multivariable Logistic Regression Analysis ◽  
Ecog Performance Status ◽  
Disease Characteristics ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

88 Background: Abiraterone acetate (AA) is typically administered with prednisone (P) to prevent symptoms of mineralocorticoid excess in patients with metastatic castrate resistant prostate cancer (mCRPC). After biochemical progression on AA + P, there is a sizeable subset of patients who have a renewed PSA response when switched from P to dexamethasone (D). The purpose of this study was to delineate clinical and pathologic factors that are predictive of a PSA response to such a steroid switch. Methods: We performed a retrospective analysis of 87 patients switched from AA+P to AA+D at Sunnybrook Odette Cancer Centre (Toronto, ON, Canada) between December 2012 and September 2018. Information on demographics, disease characteristics, previous treatments and performance status was collected. Response to the P to D switch maneuver was defined as a decrease in PSA by ≥30% within 12 weeks of the intervention (PSA30). Univariate logistic regression analyses were used to create a prediction model for each covariate tested, and R2 was applied for the measure of fit.Using multivariable logistic regression analysis and a backward stepwise selection procedure, we sought to identify patient and/or disease characteristics associated with a PSA30. Results: 38/87 patients (44%) experienced a PSA30. Univariate analysis showed that a favourable ECOG performance status, no prior docetaxel and no prior enzalutamide use were associated with a PSA30. On multivariable logistic regression analysis both favourable ECOG performance status and no prior enzalutamide use remained associated with a PSA30 (Table). Conclusions: A considerable proportionof patients with mCRPC who biochemically progress on AA+P have a renewed PSA response when changed to AA+D.Patients with a favourable ECOG performance status and no prior enzalutamide use are more likely to respond to such a steroid switch. Further prospective studies are needed to validate our findings.[Table: see text]

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