Skip to main content
Premium Trial:

Request an Annual Quote

Matched Therapy 'Evidence Scale' Predicts Targeted Treatment Efficacy in Breast Cancer Patients

NEW YORK — When there is strong evidence tying genetic variants to matched therapies, such targeted treatments can boost progression-free survival (PFS) times among metastatic breast cancer patients, a new study has found.

This suggested to the Institut Curie-led team that scales of evidence for target actionability like the European Society of Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) used in the study can inform treatment decisions and affect patient outcomes.

The SAFIR02-BREAST trial, a Phase II randomized trial investigating the use of genomic analysis as a therapeutic decision tool, compared the efficacy of maintenance chemotherapy to targeted therapies to better understand how genomic profiling can inform therapeutic decisions.

Using data from that study, the researchers found that when genomic variants are classified as level I or II alterations on ESCAT — meaning there was either evidence or preliminary evidence that a matched drug was efficacious — then targeted treatments lead to better PFS. Other genomic alteration-drug matches with limited supporting evidence on that scale had no effect on PFS.

"Reporting the results of genomics in the context of a framework of target actionability should therefore be considered as a standard of care," the researchers led by Institut Curie's Ivan Bièche wrote in their paper.

The new study, which was funded in part by AstraZeneca, appeared on Wednesday in Nature. First author Fabrice André from the Institute Gustave Roussy previously reported results from the analysis at the 2021 San Antonio Breast Cancer Symposium.

Of the 1,462 patients in the SAFIR02-BREAST trial with HER2-negative metastatic breast cancer, 646 individuals were found to have a targetable genomic alteration. Then, 238 patients were randomized 2:1 to either receive targeted therapy matched to their genomic profile or maintenance chemotherapy.

In this arm of the study, 115 patients had a genomic alteration classified as ESCAT I/II. Most of these patients had BRCA1 or BRCA2 alterations, though others had AKT1, PTEN, or other mutations. Patients with hotspot PIK3CA mutations, meanwhile, were randomized 2:1 to either receive alpelisib and fulvestrant or maintenance chemotherapy.

After a median follow-up of 21.4 months, patients with ESCAT I/II genomic alterations had significantly longer PFS when receiving a targeted therapy, as compared to maintenance chemotherapy, 9.1 months to 2.8 months.

Within the ESCAT I/II group, the researchers further found no difference in efficacy of matched targeted therapies between patients with ESCAT I versus ESCAT II genomic alterations and reported that ESCAT classification could predict efficacy of the matched targeted treatment.

Targeted therapies, however, were not effective in patients without ESCAT I or II-level genomic alterations.

The researchers noted that many of the patients in their study harbored BRCA mutations, and that patients with germline changes often derive high benefit from matched targeted therapies and could skew their analysis. But after excluding patients with germline BRCA1 or BRCA2 mutations, the researchers still noted a reduced risk of disease progression.

Based on this, the researchers said ESCAT and possibly other frameworks like those from the Association for Molecular Pathology and OncoKB could aid in the clinical interpretation of sequencing results. They further argued for additional investment in databases to inform clinicians of the efficacy of matched mutation-drug therapies.

Bièche and colleagues cautioned, though, that DNA sequencing alone is not enough to identify treatment targets for all cancer patients and suggested that future efforts could combine various data sources, such as DNA sequencing, RNA expression, and organoid modeling data.