Predictive factor of androgen deprivation therapy for patients with advanced stage prostate cancer

Kongseang, Chaiyut; Attawettayanon, Worapat; Kanchanawanichkul, Watid; Pripatnanont, Choosak

doi:10.1016/j.prnil.2017.01.004

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…For some patients in this cohort, it would not be unreasonable to commence ADT as monotherapy. Initial predictive factors to response, such as starting PSA value, presence of symptoms and PSA nadir level, can guide further decision-making and prognostication [ 52 ]. Some oncologists argue that treatment intensification can be added later if the PSA is not adequately suppressed with initial ADT.…”

Section: Tailoring Treatment Aims To the Individual Goalmentioning

confidence: 99%

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting

Smith

Shamash

2020

Oncol Ther

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The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has changed radically in recent years. Androgen deprivation therapy (ADT) alone was for decades the standard of care for treating mHSPC. This changed when studies showed that the addition of docetaxel chemotherapy or abiraterone acetate to ADT significantly increases overall survival of patients with mHSPC, followed by more recent evidence showing the efficacy of androgen receptor antagonists, such as enzalutamide and apalutamide, in this setting. While this rapid therapeutic evolution is welcome, it presents clinicians with a crucial challenge: the choice of treatment selection and sequencing. In the first-line setting there are no comparative data currently available to guide treatment choice between the different available regimens, and no prospective data to guide clinical decision after progression. Decisions on treatment will now need to be personalised based on indirect comparison of the available efficacy data from multiple phase 3 studies, together with considerations of disease volume, comorbidities, treatment aims, toxicity profile and cost reimbursement within the healthcare setting. Here, we provide an overview of the clinical trial data to date and propose some biological and clinical insights which may be helpful in making decisions on treatment selection and sequencing.

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Section: Tailoring Treatment Aims To the Individual Goalmentioning

confidence: 99%

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting

Smith

Shamash

2020

Oncol Ther

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“…Most of these predictive models were developed using multivariate analysis that provides very little biological insight on the relationship between identified predictors and disease progression [8][9][10][11][12]. Several PSA kinetic parameters such as time to PSA nadir and PSA nadir level have been shown to be significant predictors of disease progression for PCa patients receiving ADT [9][10][11]. However, the complex quantitative relationship between clinical predictors and PSA kinetics and disease progression in ADT-treated PCa patients remains largely unknown.…”

Section: Plos Onementioning

confidence: 99%

“…However, the majority of patients eventually progress to a castration-resistant state, and it was estimated that the response to ADT typically lasts 14 to 20 months in metastatic PCa [5,6], and the duration of response to ADT is variable among patients [7]. A few studies have examined clinical factors that predict the time to castration resistance for patients on ADT [8][9][10][11][12], but the detailed timedependent profile of tumor regression and/or growth in patients with hormone-sensitive PCa on medical ADT has never been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

Using medical claims database to develop a population disease progression model for leuprorelin-treated subjects with hormone-sensitive prostate cancer

et al. 2020

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Androgen deprivation therapy (ADT) is a widely used treatment for patients with hormonesensitive prostate cancer (PCa). However, duration of treatment response varies, and most patients eventually experience disease progression despite treatment. Leuprorelin is a luteinizing hormone-releasing hormone (LHRH) agonist, a commonly used form of ADT. Prostate-specific antigen (PSA) is a biomarker for monitoring disease progression and predicting treatment response and survival in PCa. However, time-dependent profile of tumor regression and growth in patients with hormone-sensitive PCa on ADT has never been fully characterized. In this analysis, nationwide medical claims database provided by Humana from 2007 to 2011 was used to construct a population-based disease progression model for patients with hormone-sensitive PCa on leuprorelin. Data were analyzed by nonlinear mixed effects modeling utilizing Monte Carlo Parametric Expectation Maximization (MCPEM) method in NONMEM. Covariate selection was performed using a modified Wald's approximation method with backward elimination (WAM-BE) proposed by our group. 1113 PSA observations from 264 subjects with malignant PCa were used for model development. PSA kinetics were well described by the final covariate model. Model parameters were well estimated, but large between-patient variability was observed. Hemoglobin significantly affected proportion of drug-resistant cells in the original tumor, while baseline PSA and antiandrogen use significantly affected treatment effect on drug-sensitive PCa cells (Ds). Population estimate of Ds was 3.78 x 10 −2 day-1. Population estimates of growth rates for drugsensitive (Gs) and drug-resistant PCa cells (G R) were 1.96 x 10 −3 and 6.54 x 10 −4 day-1 , corresponding to a PSA doubling time of 354 and 1060 days, respectively. Proportion of the original PCa cells inherently resistant to treatment was estimated to be 1.94%. Application of population-based disease progression model to clinical data allowed characterization of tumor resistant patterns and growth/regression rates that enhances our understanding of how PCa responds to ADT.

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Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms

Tukachinsky

Madison

Chung

et al. 2021

Clinical Cancer Research

120

133

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Purpose: Comprehensive genomic profiling (CGP) is of increasing value for patients with metastatic castration-resistant prostate cancer (mCRPC). mCRPC tends to metastasize to bone, making tissue biopsies challenging to obtain. We hypothesized CGP of cell-free circulating tumor DNA (ctDNA) could offer a minimally invasive alternative to detect targetable genomic alterations (GA) that inform clinical care. Experimental Design: Using plasma from 3,334 patients with mCRPC (including 1,674 screening samples from TRITON2/3), we evaluated the landscape of GAs detected in ctDNA and assessed concordance with tissue-based CGP. Results: A total of 3,129 patients (94%) had detectable ctDNA with a median ctDNA fraction of 7.5%; BRCA1/2 was mutated in 295 (8.8%). In concordance analysis, 72 of 837 patients had BRCA1/2 mutations detected in tissue, 67 (93%) of which were also identified using ctDNA, including 100% of predicted germline variants. ctDNA harbored some BRCA1/2 alterations not identified by tissue testing, and ctDNA was enriched in therapy resistance alterations, as well as possible clonal hematopoiesis mutations (e.g., in ATM and CHEK2). Potential androgen receptor resistance alterations were detected in 940 of 2,213 patients (42%), including amplifications, polyclonal and compound mutations, rearrangements, and novel deletions in exon 8. Conclusions: Genomic analysis of ctDNA from patients with mCRPC recapitulates the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 mutations, but more acquired resistance alterations detected in ctDNA. CGP of ctDNA is a compelling clinical complement to tissue CGP, with reflex to tissue CGP if negative for actionable variants. See related commentary by Hawkey and Armstrong, p. 2961

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Predictive factor of androgen deprivation therapy for patients with advanced stage prostate cancer

Cited by 4 publications

References 22 publications

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting

Using medical claims database to develop a population disease progression model for leuprorelin-treated subjects with hormone-sensitive prostate cancer

Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms

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