Genomics can improve patients outcomes in metastatic breast cancer – with the right tools

9 Dec 2021

Dr Fabrice André

Genomics can help guide treatment and improve outcomes in metastatic breast cancer patients, but only if interpreted with a validated framework of actionability, oncologists have told the 2021 San Antonio Breast Cancer Symposium.

A study presented by Dr Fabrice André, research director at Gustave Roussy Cancer Campus, Paris, which assessed the efficacy of therapies in relation to their ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) ranking found personalised therapies were only effective when matched to ‘tier I/II’ genomic alterations.

The study featured 238 metastatic breast cancer patients with stable disease after six to eight cycles of chemotherapy and known genomic alterations who received targeted therapies or maintenance chemotherapy.

Of those with ESCAT I/II genomic alterations, patients who received matched therapies associated with improved outcomes in clinical trials (tier I) or anti-tumour activity but unknown magnitude of benefit (tier II) achieved median 9.1 months’ progression free survival (PFS) while those on maintenance chemotherapy reached 2.8.

Overall, however, PFS for patients on therapies matched to genomic alterations of any ESCAT tier versus maintenance chemotherapy was not significantly different. Additionally, targeted therapies were not effective when matched to non-ESCAT I/II alterations, suggesting that the classification was “highly predictive of the benefits of targeted therapies matched to genomic alterations”, a statement read.

“Our study showed that genomic analysis improves the outcome of patients with metastatic breast cancer if they carry alterations classified as ESCAT I/II,” Professor André said.

“These findings suggest that genomics should be a part of the pathway of care, but it has no impact if the results are not interpreted using a validated framework of actionability of the gene alterations identified.”

In his virtual presentation to the meeting, Dr André flagged that failing to use such a framework and include the level of evidence for mutations in a genomic report could mean “we take the risk of providing a targeted therapy that does not match, that is not effective and that the patient could be undertreated”.

While the number of targeted therapies matched to genomic alterations is limited, the library of known mutations is growing. During his study, Professor André and his team identified 21 gene amplifications or deletions associated with metastatic evolution, poor prognosis and drug resistance or sensitivity.

With the right tools to interpret this information, precision medicine could improve patient outcomes, he concluded.

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