Patients with metastatic breast cancer had improved outcomes with the use of multigene sequencing as a therapeutic decision tool when identified genomic alterations were ranked in the I/II tiers of the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), according to results of the SAFIR02-BREAST trial.

These results indicate that genomic profiling has clinical utility in patients with metastatic breast cancer “only when the decision to administer targeted therapy is driven by a validated framework of actionability,” according to Fabrice André, MD, PhD, research director at Gustave Roussy Cancer Center in Villejuif, France, who presented the results at the 2021 San Antonio Breast Cancer Symposium (SABCS).

SAFIR02-BREAST ( Identifier: NCT02299999) is a phase 2 trial that included 1462 patients with metastatic, HER2-negative breast cancer. The trial was designed to evaluate whether targeted therapies guided by genomics improved progression-free survival (PFS) compared with maintenance chemotherapy. Patients who had received more than 2 lines of chemotherapy or 1 of the targeted therapies evaluated in the trial were not eligible.

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Dr André and colleagues performed a pooled analysis of this trial and the SAFIR-PI3K trial that compared alpelisib and fulvestrant with maintenance chemotherapy in patients with PIK3CA-mutated metastatic breast cancer.

They performed genomic analysis through next-generation sequencing and single nucleotide polymorphism array. Next, the researchers assigned 238 patients whose disease was stable after 6 to 8 cycles of chemotherapy and who carried known genomic alterations to either the appropriate targeted therapies matched to their genomic alteration (157 patients) or maintenance chemotherapy (81 patients).

Vistusertib, AZD4547, capivasertib, sapitinib, selumetinib, vandetanib, bicalutamide, olaparib, and alpelisib were the drugs included in the study, and these drugs were matched to the following targets respectively: mTOR, EGFR, AKT, HER2 or EGFR, MEK, VEGF or EGFR, androgen receptor, and PARP.

The researchers found that targeted therapies matched to genomic alterations in ESCAT tier I/II significantly improved PFS. ESCAT tier I is where the alteration/drug match is associated with improved outcomes in clinical trials, and tier II is where the alteration/drug match is associated with antitumor activity, but the magnitude of benefit is unknown.

In the patients with an ESCAT I/II genomic alteration, the median PFS was 9.1 months in the matched targeted therapy arm and 2.8 months in the maintenance chemotherapy arm (hazard ratio, 0.41; P <.001).

Because this was statistically significant, the researchers then tested the use of targeted therapy in the overall population. In that analysis, there was no significant improvement in PFS for targeted therapy compared with maintenance therapy, suggesting that the ESCAT classification was predictive of the benefit of targeted therapy matched to genomic alterations.

Based on these results, Dr André concluded that patients should be offered genomic testing to detect ESCAT tier I/II alterations.

Disclosures: This research was supported by Fondation ARC, Breast Cancer Research Foundation, and Agence Nationale de la Recherche (IHU-B). Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


André F, Goncalves A, Filleron T, et al. Clinical utility of molecular tumor profiling: Results from the randomized trial SAFIR01-BREAST. Presented at SABCS 2021; December 7-10, 2021; San Antonio, TX. Abstract GS1-10.

This article originally appeared on Cancer Therapy Advisor