Decipher GRID ‘Signature’ Predicts Chemo Benefits in HSPC, Research Shows

Decipher GRID ‘Signature’ Predicts Chemo Benefits in HSPC, Research Shows
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Decipher Bioscience’s proprietary artificial intelligence platform, Decipher GRID, one of the world’s largest urologic cancer genomic databases, can be used to identify subtypes of prostate cancer and predict which men may benefit from treatment with chemotherapy, according to clinical data using the technology.

Its use helped determine that men newly diagnosed with a specific subtype of metastatic hormone-sensitive prostate cancer (mHSPC) would benefit more from androgen deprivation therapy (ADT) when the treatment was combined with taxane-based chemotherapy.

“Identifying which patients will benefit from chemotherapy is one of the most important clinical questions in the management of metastatic prostate cancer,” Christopher Sweeney, MBBS, a cancer-specialized clinician and professor of medicine at Dana-Farber Cancer Institute, said in a press release.

“The ability to identify these patients at diagnosis is a very important step towards improving patient outcomes and accelerating the inclusion of novel [treatments] into the standard of care,” Sweeney said.

The data, “Luminal B subtype as a predictive biomarker of docetaxel benefit for newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A correlative study of E3805 CHAARTED,” were presented at the 2020 Genitourinary Cancer Symposium, held recently in San Francisco.

mHSPC, also known as metastatic castration-sensitive prostate cancer (mCSPC), refers to prostate cancer that has spread to other parts of the body but still responds to androgen deprivation therapy. The goal of ADT  is to reduce the levels of male hormones, called androgens, in the body, to stop them from fueling prostate cancer cells.

Even with ADT, however, this type of prostate cancer is usually associated with poor outcomes.

The standard of care for men with mHSPC is ADT, which can be combined with a systemic therapy, including taxane-based chemotherapy. Such chemo uses taxane, which blocks cell growth by stopping cell division.

However, determining the optimal treatment in this patient population remains challenging.

It is thus crucial to identify biomarkers that can predict treatment responses early on. That allows clinicians to distinguish which patients will benefit more from adding a systemic therapy to ADT and potentially improve their survival.

The Decipher Genomic Resource for Intelligent Discovery, or Decipher GRID, is one of the largest urologic cancer genomic databases in the world. Developed by Decipher Biosciences, formerly known as GenomeDx Biosciences, it can be used to identify subtypes of prostate cancer, namely luminal B, luminal A, and basal subtypes.

This technology has the potential to improve the diagnosis, prognosis, and treatment of prostate cancer, aiding in the development of therapy regimens tailored for individual patients.

Analysis with the Decipher GRID has shown that patients with specific molecular subtypes have different responses to systemic therapies. Preclinical models predict that prostate cancer patients with a luminal subtype may respond better to taxane-based chemotherapy than men with a basal subtype.

Moreover, the CHAARTED Phase 3 clinical trial (NCT00309985) showed that those with high-risk features benefited more from the combination than the single therapy. The study had evaluated whether adding docetaxel chemotherapy to ADT was superior to ADT alone in treating men newly diagnosed with mHSPC,

Now, the researchers evaluated the predictive value of this molecular subtype signature — luminal B, luminal A, or basal — in men who participated in the CHAARTED study. Using the Decipher GRID molecular signature, the team determined the tumor’s molecular subtype in 160 men out of the 198 with available tumor tissue.

The results showed that the tumors of 80 men (50%) were classified as luminal B, with those of 77 patients (48%) identified as basal. The tumors of three men (2%) were classified as luminal A. In addition, among patients receiving ADT alone, the luminal B subtype was significantly associated with a shorter survival, compared with the basal subtype.

Notably, men with the luminal B subtype benefited most from adding docetaxel to ADT, while men with the other two subtypes experienced no significant survival benefits with the combination treatment. Luminal B patients receiving the combination lived for a median of 22 months longer than those receiving ADT alone, reflecting a 55% reduction in their risk of death.

These data suggest that the Decipher GRID molecular subtyping signature can be used to successfully predict which mHSPC patients may benefit from the addition of taxane-based chemotherapy to ADT.

The team noted that they plan to validate these findings in clinical trials with groups of patients distinguished by these subtype signatures.

Data from nine other studies of Decipher tests also were presented at the symposium.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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