TEST:

Prolaris®

"Myriad Genetics, Inc...announced that its Prolaris prostate cancer prognostic test continues to be classified by the National Comprehensive Cancer Network (NCCN) as an ‘Advanced Tool’ in the fight against prostate cancer. Like other gene expression-based tests, Prolaris for many years has been included in NCCN guidelines with category 2A level of evidence, meaning its inclusion has support from at least 85% of members on the NCCN prostate panel."

Prolaris added significant information to clinical risk stratification to aid in treatment decision making. Intermediate-risk prostate cancer patients who were recommended to AS by Prolaris were more likely to initially pursue AS and were more likely to remain on AS at 3 years post-diagnosis than patients recommended to DT.

PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice.

"Eurobio Scientific...announces the finalisation of its agreement with Myriad Genetics to acquire the EndoPredict genomic test. As part of the agreement announced on 7 May 2024...on 1 August 2024 the Group has completed the acquisition of the second-generation genomic test EndoPredict for breast cancer and the license agreement to distribute the second-generation genomic test Prolaris for prostate cancer from Myriad Genetics. Revenues from these two activities are around €8m on an annual basis, with EBITDA levels in the short and medium term diluting the Group's performance."

"Active surveillance has emerged as a preferred strategy for managing low-risk prostate cancer, and tissue-based biomarkers play a crucial role in refining patient selection and risk stratification. Standardization and validation of these biomarkers are essential to ensure their widespread clinical use and optimize patient outcomes."

"Myriad Genetics...announced that JCO Precision Oncology has published a study showing a clinical cell-cycle risk (CCR) score can accurately predict the benefit of adding androgen deprivation therapy (ADT) to radiation therapy (RT) in men with localized prostate cancer."

The precise and personalized risk estimate of metastasis provided by the CCR score can help inform patients and physicians when considering treatment intensification.

"Myriad Genetics, Inc...announced the reorganization of its European operations to better align company resources to its domestic opportunities while continuing to serve key biopharma partners and patients outside the United States."

AS is an option for favorable prostate cancer. We show that there was no difference in Biomarkers, PIRADS, and PSAD between the treated and the AS group. Escalation to treatment from AS should be a shared decision making between provider and patient.

Unfortunately, methods within clinical routine today do not allow molecular subclassification of prostate cancer. To enable comparison of the most promising treatment-predictive biomarkers and to evaluate the health economic value of implementing such precision medicine for prostate cancer, a prospective study is being planned as a joint initiative in Sweden that aims to evaluate and validate biomarkers and to establish a study platform for adaptive biomarker-driven clinical trials (sprintr.se).

P=N/A | N=900 | Recruiting | Sponsor: University of Michigan Rogel Cancer Center | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Jul 2025

Our analysis indicates a growing trend in the utilization of tissue-based genomic testing for PCa. Nevertheless, they are utilized in less than 2% of PCa patients, whether at initial diagnosis or after surgical treatment. Although it is anticipated that their use may increase as more scientific evidence becomes available, their role requires further elucidation.

45th Annual Raymond James Institutional Investors Conference

DL algorithms utilizing WSI with or without clinical-pathologic parameters outperform currently employed genomic classifiers for the prediction of metastasis. Validation in additional multi-institutional and racially diverse cohorts is underway.

GCs did not substantially improve a clinical prediction model for UG/US, a short-term and imperfect surrogate for clinically relevant disease outcomes.

P=N/A | N=900 | Recruiting | Sponsor: University of Michigan Rogel Cancer Center | Trial completion date: Nov 2023 ➔ Jul 2024 | Trial primary completion date: Nov 2023 ➔ Jul 2024

"Genomic classifiers provide a small but consistent improvement upon the prognostic ability of clinical classification schemes, which may be helpful when treatment decisions are uncertain. However, evidence from current management-era data and of the predictive ability of these tests is needed."

P=N/A; Phase classification: P3 --> P=N/A

For patients with NCCN intermediate-risk PCa who were identified by genomic testing as candidates for AS, AS is safe based on the very low observed metastasis risk. The CCR score is a strong predictor of metastasis beyond clinicopathologic factors.

DL algorithms utilizing WSI with or without clinical-pathologic parameters outperform currently employed genomic classifiers for the prediction of metastasis. Validation in additional multi-institutional and racially diverse cohorts is underway.

"Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management."

Our findings are congruent with other studies in highlighting the high degree of multifocality and bilateral disease in men with prostate cancer. GRS did not improve our ability to select for focal disease. This emphasizes the importance of continuing to work to improve patient selection parameters for focal therapy.

"There is minimal to moderate correlation between the 22-GC and GPS or CCP gene expression signatures tested. Therefore, these tests should not be viewed as interchangeable, and utilization should be based on the level of evidence supporting each gene expression biomarker."

"Our data reveals that MRI-visible csPCas harbor more aggressive histomic and transcriptomic features than MRI-invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI."

"There is minimal to moderate correlation between the 22-GC and GPS or CCP gene expression signatures tested. Therefore, these tests should not be viewed as interchangeable, and utilization should be based on the level of evidence supporting each gene expression biomarker."

"Myriad Genetics, Inc...announced the integration of Absolute Risk Reduction (ARR) into the Prolaris^® Prostate Cancer Prognostic Test to help patients and providers make personalized treatment decisions regarding hormone therapy. Prolaris is the only biomarker test to quantify the benefits of adding androgen deprivation therapy (ADT) to radiation therapy (RT)."

"Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited."

Mycophenolate mofetil was switched to everolimus, and he was referred to dermatology...Before he could pursue recommended treatments, he was admitted in November 2021 for fever, worsening back pain, leukocytosis (WBC 131.6 thousand/µL; increased from 7.3 thousand/µL in October 2021), anemia (6 gm/dL), and thrombocytopenia (17 thousand/µL)... Chronic immunosuppression impairs anti-tumor immune surveillance and has a central role in oncogenesis after solid organ transplant. LT recipients receive even more immunosuppression. Immunosuppression modification with mammalian target of rapamycin inhibitors (everolimus) may interfere with cancer cell proliferation and angiogenesis.

The Prolaris test can accurately predict an individual's benefit of adding ADT to RT, and the risk threshold is consistent with patient attitudes about when to use or omit ADT. 1. Spratt DE, Tward JD: IJROBP 108:899-902, 2020.

P3; Trial primary completion date: Dec 2021 --> Aug 2026

The utilization of tissue-based genomic testing increased rapidly after 2017 among newly diagnosed prostate cancer patients with commercial or Medicare supplemental insurance. There was wide variation across metropolitan regions, suggesting local coverage decision and provider factors may carry influence over use of these tests. Future studies should evaluate the impact of provider factors and the economic implications of incorporating these tests for risk-stratification.

Use of tissue-based genomic testing is associated with significant expense. Despite this expense, their use was associated with similar total payments across treatment groups, with the greatest savings ($119) in Medicare patients receiving RT and the greatest expense in Medicare patients undergoing RP ($494).

Also, the PPS showed to distinguish between normal prostate tissue, hyperplasia, and PCa. Results suggest that these biomarkers could serve as a tool for the risk classification of indolent and aggressive PCa tumors.

"CCR-based thresholds provided a more personalized risk which may result in different management compared to risk categories defined by NCCN FI- and UFI- prostate cancer."

In this study, the largest to date to assess the clinical utility of the AS threshold in NCCN intermediate risk men, patients with CCR-based mortality risk below the AS threshold were more likely to initially select AS compared to patients with scores above the threshold. Additionally, patients with CCR-based mortality risk below the AS threshold experienced higher durability of AS. Together, these findings demonstrate that Prolaris provides important clinical information that significantly impacts treatment decisions in patients with NCCN favorable- and unfavorable-intermediate risk prostate cancer.

Conclusions Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers.

"Myriad Genetics, Inc...announced the launch of UroSuite, a comprehensive suite of genetic risk assessment tests that cover every stage of prostate cancer care....UroSuite includes Myriad’s Prolaris® Prostate Cancer Test, MyRisk™ Hereditary Cancer Test, BRACAnalysis CDx^® and Precise™ Tumor Molecular Profile Test. The combination of tests provides integrated genetic insights and makes it easier to tailor therapy and clinical trial selection for patients....'Today’s launch of UroSuite reinforces Myriad Genetics’ commitment to advancing health and well-being for all through a set of testing solutions for prostate cancer care, best-in-class support, and access to genetics and cancer specialists,' said Paul J. Diaz, president and CEO, Myriad Genetics."

Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers.

PATIENT SUMMARY: A number of tests are available for measuring expression levels of genes related to prostate or bladder cancer. We review the usefulness of these tests in stratifying risk for patients and predicting their prognosis.

P=N/A; Trial completion date: Sep 2027 --> Jan 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2022 --> Jan 2022; There is sufficient follow-up data to meet the endpoints of the study.

P=N/A; Trial completion date: Jan 2024 --> Mar 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2024 --> Mar 2022; Myriad has sufficient data to do an analysis on the primary objective, durability, and has made the decision not to continue collecting data for the other study objectives.

P=N/A; Trial completion date: Oct 2022 --> Dec 2024 | Trial primary completion date: Sep 2022 --> Nov 2024