Genomic-Based Targeted Therapy Improved PFS for Certain Metastatic Breast Cancers

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 SAFI02-BREAST trial presented at the 2021 San Antonio Breast Cancer Symposium (SABCS).

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 Campus, who presented the results.

SAFIR02-BREAST 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 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.

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.


Continue Reading

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: m-TOR, 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 progression-free survival.

ESCAT tier I is where alteration/drug match is associated with improved outcome in clinical trials and tier II is where alteration/drug match is associated with antitumor activity but the magnitude of benefit is unknown.

In this population, targeted therapy based on genomic alteration resulted in a median profession-free survival of 9.1 months compared with 2.8 months (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 progression-free survival 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.

Disclosure: This research was supported by Fondation ARC, Breast Cancer Research Foundation, 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.

Reference

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.

Source: Medical Bag https://www.medicalbag.com/home/news/breast-cancer-genomic-therapy-improves-survival-risk-safir02/

Breast Cancer General News