Prostate Cancer: Predictive Markers in Clinical Development

2012 ◽  
pp. 69-103
Author(s):  
Courtney K. Phillips ◽  
Daniel P. Petrylak
Keyword(s):  
Prostate Cancer ◽  
Clinical Development ◽  
Predictive Markers

scholarly journals Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Briones ◽  
Maira Khan ◽  
Amanjot K. Sidhu ◽  
Liying Zhang ◽  
Martin Smoragiewicz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Predictive Factors ◽  
Real World ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Markers ◽  
Age At Diagnosis ◽  
Free Survival ◽  
Significant Difference

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

Endothelin receptor antagonists: Rationale, clinical development, and role in prostate cancer therapeutics

2006 ◽  
Vol 8 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Snehal G. Thakkar ◽  
Toni K. Choueiri ◽  
Jorge A. Garcia
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapeutics ◽  
Clinical Development ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists

Serum proteomics guided discovery of predictive biomarkers of response to androgen ablation (AA) in prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 104-104
Author(s):  
Manish Kohli ◽  
Ann L. Oberg ◽  
Douglas W. Mahoney ◽  
Shaun M Riska ◽  
Roman M Zenka ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Proteomic Analysis ◽  
Predictive Biomarkers ◽  
Cox Proportional Hazards ◽  
Predictive Markers ◽  
Differentially Expressed ◽  
Androgen Ablation ◽  
Serum Proteomics ◽  
Median Change

104 Background: Currently there are no serum predictive markers of response to AA. We used a proteomic based analytic approach to identify candidates. Methods: Serum from three non-localized prostate cancer cohorts was analyzed. The first included15 paired untreated hormone-sensitive “pre-AA” and 3-month “post-AA” specimens; the second included 10 “early AA failure” (median time to AA failure:11 months) and the third included 10 “late AA failure” specimens (median time to AA failure: 95 months). Proteomic analysis was performed with isobaric mass tags for relative and absolute quanititation (iTRAQ) analyzed by reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Differentially expressed candidate proteins were identified by comparisons of (i) paired pre/post-AA proteomes and (ii) post-AA proteome with the combined AA failure cohorts at a False Discovery Rate of 0.2. ELISA assays were used to verify candidate markers in a second stored aliquot of first cohort specimens. This cohort was followed for AA failure. Association of post-AA ELISA levels of candidate markers with time to AA failure was performed using Cox proportional hazards regression, summarized as relative risk (RR) for AA failure. Results: Median PSA in pre/post-AA first cohort were 3.15 ng/ml and 0.29 ng/ml. Median PSA in the second and third cohorts were 27.3 and 4.3 ng/ml. Between post-AA and AA failure cohorts, 149 proteins were differentially expressed. Between early and late AA failure 98 proteins were differentially expressed; 47 proteins were common in both comparisons. ELISA assays verified expression levels of 2/47 proteins in the first cohort; zinc alpha-2 macroglobulin (ZAG), and Neuropilin-2 (NPL2). Median change in ZAG decreased by 2073.5 ng/ml (post versus pre-AA) while median change in NPL2 levels increased by 2.9 ng/ml. After a median follow-up of 43 months from the post-AA time-point, 4/15 first cohort subjects had failed AA. The RR of AA failure for ZAG levels below the median change was 3.8 (95% CI: 0.4-37) and 3.0 (95% CI: 0.3-29) for NPL2. Conclusions: A global proteomic analysis identified ZAG and NPL2 as candidate serum predictive markers of AA response which needs further validation.

Drugs in Clinical Development for Prostate Cancer

2011 ◽  
Vol 25 (6) ◽  
pp. 387-404 ◽  
Keyword(s):  
Prostate Cancer ◽  
Clinical Development

scholarly journals PSCA, Cox-2, and Ki-67 are independent, predictive markers of biochemical recurrence in clinically localized prostate cancer: a retrospective study

2017 ◽  
Vol 19 (4) ◽  
pp. 458 ◽  
Author(s):  
KangHyun Lee ◽  
SungHan Kim ◽  
WeonSeo Park ◽  
BoRam Park ◽  
Jungnam Joo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Study ◽  
Biochemical Recurrence ◽  
Predictive Markers ◽  
Localized Prostate Cancer ◽  
Ki 67 ◽  
Cox 2

Castration-resistant Prostate Cancer – Chemotherapies and Molecular Targets

2013 ◽  
Vol 09 (01) ◽  
pp. 27
Author(s):  
Amit Bahl ◽  
Keyword(s):  
Prostate Cancer ◽  
Survival Rates ◽  
Signal Transduction Pathway ◽  
Molecular Targets ◽  
Abiraterone Acetate ◽  
Clinical Development ◽  
Transduction Pathway ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Castration-resistant prostate cancer has a poor prognosis: current chemotherapeutic approaches ultimately result in resistance and are associated with survival rates of less than 2 years. However, the last decade has seen an expansion in the number of therapeutic options for CRPC and the regulatory approval of several agents, including the chemotherapy drug cabazitaxel and the targeted agents abiraterone acetate, enzalatumide and denosumab. Novel targeted agents inhibit androgen receptor-mediated signalling, and non-hormonal targets, including apoptosis, signal transduction pathway inhibitors, angiogenesis and bone and immune microenvironments. Clinical trials of these agents, however, have demonstrated varied efficacy. Among the drugs in clinical development, custirsen, cabozantinib and dasatinib are among the most promising. There is a requirement for studies directly comparing agents, and for improved patient selection to identify patients benefitting from a particular therapy.

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