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Genomic Profiling Improves Outcomes in Breast Cancer

— PFS was better when targeted treatment for genomic alterations was supported by ESCAT criteria

MedpageToday

SAN ANTONIO -- Use of genomic profiling supported by validated criteria, such as the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), can help improve outcomes in patients with metastatic breast cancer, according to a pooled analysis of the and trials.

In 115 patients presenting with an ESCAT I/II alteration, median progression-free survival (PFS) was 9.1 months with use of targeted therapy matched to genomic alterations compared with 2.8 months with use of maintenance chemotherapy (adjusted HR 0.41, 90% CI 0.27-0.61, P<0.001), reported Fabrice André, MD, PhD, of Gustave Roussy Cancer Campus in Villejuif, France, during a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS).

However, there was no statistically significant difference when the investigators evaluated the entire population of 238 patients. In this population, the PFS with targeted therapy matched to genomic alterations was 5.5 months compared with 2.9 months with maintenance chemotherapy (adjusted HR 0.77, 95% CI 0.56-1.06, P=0.109).

Targeted therapies matched to genomic alterations were not effective in patients without ESCAT I/II alteration (HR 1.15, 95% CI 0.76-1.75), André and team noted.

"I cannot overstate how important this clinical trial is," said discussant Virginia Kaklamani, MD, of UT Health San Antonio in Texas.

"This is the first trial that we have where we used genomic alterations to actively change a patient's treatment plan and we have found an improvement in the patient's outcomes," she continued. "What we are trying to do, and which Dr. André showed so eloquently, is that by finding changes in the tumor unique to that patient, and by having targeted therapies available for that change, we're able to treat that patient with that specific targeted therapy, instead of standard of care, which would have been chemotherapy, and improve the patient's outcome."

"I think this is something we are going to be using more and more," she added.

The phase II SAFIR02-BREAST trial enrolled patients with metastatic HER2-negative breast cancer to evaluate whether targeted therapies guided by genomics improved PFS compared with maintenance chemotherapy. Patients who had received more than two lines of chemotherapy or one of the targeted therapies evaluated in the trial were not eligible to participate.

SAFIR-PI3K compared a combination of the PI3Kα-specific inhibitor alpelisib (Piqray) and the estrogen receptor antagonist fulvestrant with maintenance chemotherapy in patients with PIK3CA-mutated metastatic breast cancer.

The current analysis involved 1,462 patients from the two trials who underwent next-generation sequencing and then received six to eight cycles of chemotherapy.

Of these patients, 238 who had stable disease and who carried known genomic alterations were randomized 2:1 to receive the appropriate targeted therapies or maintenance chemotherapy.

Genomic alterations were classified using the ESCAT scale. An ESCAT tier I ranking shows that a genomic alteration-drug match was associated with improved outcomes in clinical trials, while a tier II ranking indicates the alteration-drug match was associated with antitumor activity, but that the magnitude of benefit was unknown.

"The level of ESCAT classification was highly predictive for the benefit of targeted therapy matched with genomic alterations in patients presenting with ESCAT I/II alterations," André said. "In patients who do not present with ESCAT I/II alterations, there is absolutely no benefit in using the genomic report."

In addition to testing for known genomic alterations, André and colleagues also conducted a single-nucleotide polymorphism (SNP) array analysis of 926 patients, which identified 21 genes altered more frequently in metastases as compared with primary tumors, of which TERT amplifications were associated with a poor outcome.

"Genomic reports must rank the genomic alterations according to a validated framework of actionability like ESCAT," André concluded, adding that oncologists should not administer a targeted therapy matched to a genomic alteration classified beyond ESCAT II, except in exploratory therapeutic trials.

In addition, the results "reinforce the fact that worldwide it is important that patients have access to genomics," he noted.

André acknowledged that the study did not assess the technology used to perform the genomic profiling, and that it did not directly assess the genomics in the study's overall population, since only patients presenting with a genomic alteration were randomized.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

This study was funded by Fondation ARC, Breast Cancer Research Foundation, and Agence Nationale de la Recherche.

André disclosed grants or advisory board/speaker honoraria (compensated to the hospital) from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lilly, and Novartis.

Primary Source

San Antonio Breast Cancer Symposium

André F, et al "Clinical utility of molecular tumor profiling: results from the randomized trial SAFIR02-BREAST" SABCS 2021; Abstract GS1-10.