Gene test opens the possibility of personalised prostate cancer treatment

A clinical trial conducted by UCL has shown for the first time how a commercially available gene expression test can accurately predict which patients with prostate cancer that has spread will benefit from chemotherapy with docetaxel, sparing some patients unpleasant side effects if the treatment is unlikely to help them.

 

The test is called the Decipher Prostate Genomic Classifier test and is manufactured by Veracyte, a U.S diagnostics company.

The study, which is part of the ongoing STAMPEDE phase III trial and published in Cell, is the first strong evidence that a gene expression test can help clinicians to make more personalised chemotherapy decisions for prostate cancer patients whose cancer has spread to other parts of the body (metastatic cancer).

UCLB brokered Veracyte’s collaboration with UCL, bringing  Veracyte’s expertise in profiling gene expression patterns in tumours together with UCL’s expertise in clinical trials and cancer biology.

In addition to showing for the first time that this commercially available test can predict docetaxel efficacy, the collaboration has also identified several new molecular classifiers that can help predict outcomes of patients.

This finding is significant as while docetaxel chemotherapy improves survival for some patients, it can also reduce quality of life due to its significant risk of side effects. This test may be used to identify which patients are likely to have docetaxel-sensitive tumours and live longer with docetaxel chemotherapy treatment.

The Decipher Prostate test is already widely used in the US to help identify localised prostate cancer more likely to spread. It becomes the first molecular test with clinical evidence from a randomised trial showing it can guide treatment choices for metastatic prostate cancer.

Harriet Story, Senior Business Manager for UCLB, said: “This collaboration between UCL and Veracyte demonstrates the potential of gene expression tests to revolutionise cancer treatment by identifying patients who will benefit from docetaxel chemotherapy. It’s deeply satisfying to see the outputs of this UCL research already available as a reimbursed test in the US to help metastatic prostate cancer patients receive more personalised treatment – impact made possible by UCL’s collaboration with a global diagnostics developer.”

 

Better choices

Among the 832 patients with metastatic prostate cancer, those with high Decipher Prostate test scores showed a much better reduction in risk of death after treatment with docetaxel (36%) compared to those with a low low Decipher Prostate test scores – these patients only had an 4% lower risk of death after treatment.

Professor Gert Attard, lead researcher at UCL Cancer Institute and UCLH, said: “

“By identifying which patients are most likely to have a survival benefit from chemotherapy, we can avoid unnecessary side effects and develop alternative treatments for people with metastatic prostate cancer who are unlikely to benefit.”

 

A milestone in efforts to re-classify prostate cancer into distinct groups

Treatment intensification with docetaxel, i.e. adding it to standard androgen deprivation therapy (ADT), can improve survival for some patients with metastatic prostate cancer. However, response rates vary, and clinicians have limited tools to identify who is likely to benefit and who is not. Veracyte’s Decipher Prostate test addresses this gap by providing a more personalised approach to treatment decisions.

Dr Emily Grist, a lead researcher of this study at UCL Cancer Institute, added: “One of our additional discoveries is of a signature that identifies inactivity of the tumour suppressor gene PTEN. This both predicts shorter life expectancy with hormone therapy and greater benefit from chemotherapy, as compared to those with PTEN activity.

“I believe our study is a milestone in efforts to re-classify prostate cancer into distinct molecular groups. The long-term impact will be bespoke treatments based on tumour molecular profiles that should improve outcomes for patients.”

There are around 55,100 new prostate cancer cases in the UK every year and 12,000 men are expected to die from prostate cancer this year. Prostate cancer is the second most common cause of cancer death in males in the UK, accounting for 14% of all cancer deaths in this group. Most prostate cancer deaths occur in patients who first presented with advanced or metastatic disease.