Matching breast-cancer treatments to high-value genomic alterations leads to better outcomes

Reuters Health - 10/12/2021 - Genomic analysis can improve outcomes for women with metastatic breast cancer if they carry alterations ranked in tier I or II of the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), new research indicates.

"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," Dr. Fabrice Andre, research director with Gustave Roussy Cancer Campus, in Villejuif, France, said in a press release.

"The general implication of our study is that precision medicine can improve patient outcome if it is interpreted with the right tools," he added.

The findings - based on pooled results from the SAFIR02-BREAST and SAFIR-P13K trial - were presented by Dr. Andre at the San Antonio Breast Cancer Symposium.

The SAFIR02-BREAST trial enrolled patients with metastatic, HER2-negative breast cancer to test whether targeted therapies guided by genomics improved progression-free survival (PFS) relative to maintenance chemotherapy. The SAFIR-PI3K trial compared a combination of alpelisib and fulvestrant with maintenance chemotherapy in patients with PIK3CA-mutated metastatic breast cancer.

A total of 1,462 women with metastatic HER2-negative breast cancer underwent multigene sequencing; 238 with known genomic alterations and stable disease following chemotherapy received either appropriate targeted therapies matched to their mutation or maintenance chemotherapy.

In 115 patients with an ESCAT I/II genomic alteration, median PFS was significantly longer with targeted therapy than with maintenance chemotherapy (9.1 months vs. 2.8 months), Dr. Andre reported.

In contrast, there was no significant difference in PFS between these two groups in the overall study population and targeted therapies were not effective when matched to alterations that did not rank as ESCAT I/II, suggesting that ESCAT classification may be highly predictive of which patients will benefit from targeted therapies.

"Genomic reports must rank the genomic alterations according to a validated framework of actionability and patients should be offered genomic testing to detect ESCAT I/II alterations," Dr. Andre said during a conference press briefing.

Briefing co-moderator Dr. Virginia Kaklamani of UT Health San Antonio MD Anderson Cancer Center said about SAFIR02-BREAST, "I really cannot overstate how important this clinical trial is. It's the first trial that we have where we have used genomic alterations to actively change a patient's treatment plan and we have found an improvement in the patient's outcomes."

"What Dr. Andre showed so eloquently was that by finding changes in the tumor that were unique to that patient, and by having targeted therapies available for that change, we were able to treat the patient with that specific targeted therapy instead of standard of care, which would have been chemotherapy and improve the patient's outcome," she said. "I think this is something that we're going to be using more and more in practice and really treating our patients based on those genomic alterations."

The study did not have commercial funding.

SOURCE: https://www.sabcs.org/ San Antonio Breast Cancer Symposium, held December 7-10, 2021.

By Megan Brooks



Posted on 10 December 202114 December 2021