Pembrolizumab (pembro) in heavily pretreated metastatic castrate-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 255-255
Author(s):  
Marcus Marie Moses ◽  
Elisa Ledet ◽  
Charlotte Manogue ◽  
Brian E. Lewis ◽  
Pedro C. Barata ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Median Time ◽  
Predictive Biomarkers ◽  
The Other ◽  
Panel Testing ◽  
Heavily Pretreated ◽  
Clinical Annotation ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Ctdna Analysis

255 Background: KEYNOTE-199 has shown PSA responses of 11% to pembro in mCRPC. This study aims to further evaluate pembro in heavily pre-treated mCRPC patients (pts) correlating clinical outcomes with somatic and germline mutational burden. Methods: Single-institution retrospective analysis of mCRPC pts treated with pembro with germline panel testing and baseline ctDNA analysis using Guardant360 (Redwood City, CA). Baseline clinical annotation was collected and correlated with ctDNA data and clinical outcomes; ctDNA annotations included amplification (amp) and somatic mutation (mut; allele fraction ≥0.3%). Clinical outcomes were assessed after 3 cycles defined as: PSA≥50% PSA decline) or PSA≥30 response. Results: 27 mCRPC pts were treated with pembro between Oct 2016 and June 2018, median age 69 (56-82), 70% Caucasian, 26% African-American, and 4% Other, 70% Gleason 8-10, 59% bone-only, 22% bone+tissue, and 19% bone+LN metastases, were included. Pembro was given after a median 5 CRPC therapies with a median initial PSA of 76.1 ng/mL (4.85-1160), median treatment duration of 1.4 months (0-24.3). Prior treatments include abiraterone (n = 27), enzalutamide (n = 17), docetaxel (n = 19), and provenge (n = 16). 18 pts had ctDNA testing both pre- and post-pembro with a median time from testing to pembro of 0.9 months (0-3.9) and a median time from pembro to NGS testing of 0.7 months (0-2.6). Pre-pembro NGS had the following cfDNA alterations: 74% AR (mut = 8, amp = 8, both = 4), 55% TP53, and 0% DNA repair. ctDNA allelic fraction decrease occurred in 50% (6/12) of pts with AR mutations. 55% (15/27) of pts completed ≥3 cycles of pembro with the following responses: PSA≥50 13% and PSA≥30 20%. Two PSA complete responders (CR) (PSA < 0.01) had germline pathogenic alterations (BLM or MSH2). One of these pts was bone only; the other had radiographic CR. The MSH2 germline tumor was MSI-H and lacked MSH2/MSH6 on immunohistochemistry. The other PSA CR was not assessed given limited tissue. Conclusions: 33% of pts evaluated, achieved a PSA decline of ≥30% al response or greater signifying there is a subset of mCRPC pts that can benefit from pembro. Further evaluation is necessary to determine predictive biomarkers for this patient population.

scholarly journals Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer

2018 ◽  
Vol 25 (2) ◽  
pp. 652-662 ◽  
Author(s):  
Ulka N. Vaishampayan ◽  
Izabela Podgorski ◽  
Lance K. Heilbrun ◽  
Jawana M. Lawhorn-Crews ◽  
Kimberlee C. Dobson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Bone Imaging ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

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.

Biomarker development trial of satraplatin in patients with metastatic castrate-resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 170-170
Author(s):  
Bobby Chi-Hung Liaw ◽  
Sonia Maria Seng ◽  
Matt D. Galsky ◽  
Che-Kai Tsao ◽  
Phillip G. Febbo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Genomic Analysis ◽  
Predictive Biomarkers ◽  
Cytotoxic Agents ◽  
Fourth Generation ◽  
Tissue Samples ◽  
Castrate Resistant Prostate Cancer ◽  
Pre Treatment ◽  
Castrate Resistant

170 Background: While satraplatin, a fourth generation oral platinum analogue, failed to improve overall survival (OS) in an unselected metastatic castrate-resistant prostate cancer (mCRPC) population (Sternberg, JCO 2009), anti-tumor activity was demonstrated, suggesting a “platinum-sensitive” subset of patients. Predictive biomarkers may not only select patients most likely to benefit from novel “targeted” therapies but also from standard (even discarded) cytotoxic agents. Development of predictive biomarkers in mCRPC is hampered by the fact that PC is associated with a long natural history and evolving genetic changes, highlighting the need for immediate pre-treatment metastatic tissue samples for biomarker development. In this trial, we sought to determine the feasibility of obtaining metastatic biopsies in patients with mCRPC treated with satraplatin. Methods: Docetaxel-refractory mCRPC patients underwent image-guided biopsy of metastatic lesions prior to treatment with satraplatin 80 mg/m2 PO on days 1 to 5 of a 35-day cycle and prednisone 5 mg PO twice daily. Biopsy samples are analyzed by whole exome and RNA sequencing, and peripheral blood samples are undergoing transcriptional profiling, to facilitate biomarker development. Results: Thirteen patients were enrolled with a median age of 71 (range: 55 to 80), prostate-specific antigen (PSA) of 82 ng/ml (0.04-3057), and Gleason score 8 (7 to 9). All patients received prior docetaxel, four (31%) had more than or eqaul to two prior chemotherapies, and two (15%) received abiraterone. Drug-related grade 3/4 toxicities included leukopenia (23%), neutropenia (8%), thrombocytopenia (8%), fatigue (8%), renal failure (8%), dysphagia (17%), and diarrhea (8%). A median of four cycles of satraplatin were completed, with declines of serum PSA of greater than or equal to 30% achieved in 4 of 13 patients (31%; 95% CI, 57.3 to 85.4%). Median time to PSA progression was 12.4 weeks (95% CI, 7.2 to 29.7+ weeks). Metastatic pre-treatment biopsies were collected in all study patients; genomic analysis is ongoing. Conclusions: This study confirms that satraplatin has anti-cancer activity in a subset of patients with mCRPC. Trials that require pre-treatment metastatic tumor biopsies are feasible. Analysis of the correlation between molecular signatures and treatment response will be presented at the meeting. Clinical trial information: NCT01289067.

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.

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.

Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer

2015 ◽  
Vol 26 (8) ◽  
pp. 910-911 ◽  
Author(s):  
Edoardo Francini ◽  
Anna I. Fiaschi ◽  
Roberto Petrioli ◽  
Vincenzo Bianco ◽  
Letizia Laera ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Heavily Pretreated ◽  
Castrate Resistant Prostate Cancer ◽  
Pretreated Patients ◽  
Castrate Resistant

scholarly journals Radium-223 in Heavily Pretreated Metastatic Castrate-Resistant Prostate Cancer

2016 ◽  
Vol 14 (5) ◽  
pp. 373-380.e2 ◽  
Author(s):  
Dipenkumar Modi ◽  
Clara Hwang ◽  
Hirva Mamdani ◽  
Seongho Kim ◽  
Hesham Gayar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radium 223 ◽  
Heavily Pretreated ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Impact of body composition parameters on clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with docetaxel

2016 ◽  
Vol 13 ◽  
pp. e39-e45 ◽  
Author(s):  
Samantha J. Cushen ◽  
Derek G. Power ◽  
Kevin P. Murphy ◽  
Ray McDermott ◽  
Brendan T. Griffin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Body Composition ◽  
Clinical Outcomes ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals Biomarker-Based Targeting of the Androgen-Androgen Receptor Axis in Advanced Prostate Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Manish Kohli ◽  
Rui Qin ◽  
Rafael Jimenez ◽  
Scott M. Dehm
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Predictive Biomarkers ◽  
Cancer Therapeutics ◽  
Predictive Biomarker ◽  
Abiraterone Acetate ◽  
New Drugs ◽  
Traditional Drug ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Recent therapeutic advances for managing advanced prostate cancer include the successful targeting of the androgen-AR axis with several new drugs in castrate resistant prostate cancer including abiraterone acetate and enzalutamide (MDV3100). This translational progress from “bench to bed-side” has resulted in an enlarging repertoire of novel and traditional drug choices now available for use in advanced prostate cancer therapeutics, which has had a positive clinical impact in prolonging longevity and quality of life of advanced prostate cancer patients. In order to further the clinical utility of these drugs, development of predictive biomarkers guiding individual therapeutic choices remains an ongoing challenge. This paper will summarize the potential in developing predictive biomarkers based on the pathophysiology of the androgen-AR axis in tumor tissue from patients with advanced prostate cancer as well as inherited variation in the patient’s genome. Specific examples of rational clinical trial designs incorporating potential predictive biomarkers from these pathways will illustrate several aspects of pharmacogenetic and pharmacogenomic predictive biomarker development in advanced prostate cancer therapeutics.

Use of radium-223 in heavily pretreated metastatic castrate resistant prostate cancer (mCRPC) patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 275-275
Author(s):  
Dipenkumar Modi ◽  
SeongHo Kim ◽  
Hirva Mansurali Mamdani ◽  
Clara Hwang ◽  
Hersham Gayar ◽  
...  
Keyword(s):  
Visual Assessment ◽  
Prior Therapy ◽  
Pain Scores ◽  
Radium 223 ◽  
Heavily Pretreated ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Pretreated Patients ◽  
Castrate Resistant ◽  
Post Therapy

275 Background: Ra 223 has been shown to improve overall survival in mCRPC patients with symptomatic bone metastases. Little is known about the utility of following PSA during Ra 223 therapy in heavily pretreated patients. Here we report our experience with Ra 223 in such a setting. Methods: We reviewed 26 heavily pretreated mCRPC patients who received Ra 223 at 3 institutions and evaluated the trend of PSA during treatment, the association of various demographic, clinical and biochemical variables with PSA trend, and the correlation of PSA trend with clinical outcomes. Patients received IV Ra 223 every 4 weeks with a planned total of 6 cycles. Results: Twenty six patients were treated between August 2013 and August 2014. Median age was 70 years (range 49-80); 77% (N=20) were European American (EA), 19% (N=5) were African Americans (AA), unknown for 1 patient. Prior therapy included docetaxel in 77% (N=20) of patients, cabazitaxel in 19% (N=5), enzalutamide in 65% (N=17), and abiraterone in 54% (N=14). 62% (N=16) received at least 3 prior therapies.35% (N=9) received all 6 cycles of Ra 223, while 18% (N=4) received only 1 cycle. Median alkaline phosphatase level increased from 126.0 U/L (54.0, 514.0) to 332.0 U/L (136.0, 566.0) at the end of Ra 223 therapy. Median pre-therapy PSA was 100.3 and median post-therapy PSA was 429.5. 54% (N=14) patients had >50% rise in PSA. Higher pre-therapy PSA was strongly associated with higher post-therapy PSA (Pearson’s correlation coefficient = 0.84, p <0.0001). Faster rate of rise in PSA was observed in patients with higher number of bone metastasis and those who have had prior therapy with docetaxel. The patients with >50% PSA rise had reported overall higher pain scores by visual assessment scale. Ra 223 was discontinued in 15% (N=4) patients due to myelosuppression and in 8% (N=2) due to side effects. Conclusions: All heavily pretreated patients receiving Ra 223 therapy for mCRPC showed PSA progression and reasonable tolerability. Only 35% of patients were able to receive all 6 cycles of Ra 223.

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