Appropriate framework must guide targeted therapy for metastatic breast cancer
medwireNews: Multigene sequencing identifies patients with metastatic breast cancer who will benefit from targeted therapy, but its use must be driven by a framework of actionability, show data presented at the 2021 San Antonio Breast Cancer Symposium.
Fabrice André, from Institut Gustave Roussy in Villejuif, France, reported that patients with ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) tier I or II genomic alterations who receive a drug matched to their alteration have significantly better progression-free survival (PFS) than those who receive maintenance chemotherapy, but no such benefit is observed among people with ESCAT tier III–V or tier X alterations.
In a statement to the press, he said that this finding suggests 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.”
The pooled analysis included data for 1462 participants of the SAFIR02-BREAST and SAFIR-PI3K studies who had HER2-negative metastatic breast cancer and were eligible for first- or second-line chemotherapy.
All participants initially underwent six to eight cycles of induction chemotherapy. At the end of this period, individuals without progressive disease who had an actionable genomic alteration identified by next-generation sequencing and SNParray (n=238) were randomly assigned to receive targeted therapy matched to their genomic alterations (n=157) or to maintenance chemotherapy (n=81).
Targeted therapies included vistusertib (targeting mTOR alterations), AZD4547 (FGFR), capivasertib (AKT), sapitinib (HER2 or EGFR), selumetinib (MEK), vandetanib (VEGF or EGFR), bicalutamide (androgen receptor), olaparib (PARP), and alpelisib (PIK3CA).
André and team first analyzed outcomes for the 115 individuals with ESCAT tier I or II alterations, which are those with clinical trial evidence showing that the alteration–drug match is associated with an improved clinical outcome or antitumor activity.
In this group, the risk for disease progression or death was a significant 59% lower among the participants who received targeted therapy (n=75) relative to those who received maintenance therapy (n=40), with median PFS durations of 9.1 and 2.8 months, respectively.
André noted in response to a question from the audience that this improvement “was not fully driven” by BRCA 1/2 targeted therapy.
The researchers then looked at the overall randomized population and found that, in this case, there was no significant difference in median PFS between the targeted and maintenance arms, at 5.5 and 2.9 months, respectively.
Furthermore, subgroup analyses showed that there was a “highly significant” interaction between ESCAT tier and outcome “meaning that genomics can improve outcome in patients with metastatic breast cancer [but] only in patients with ESCAT I/II genomic alterations,” André remarked.
He concluded that “patients should be offered genomic testing to detect ESCAT I/II alterations” but stressed that “an oncologist should not administer a targeted therapy matched to a genomic alteration classified beyond ESCAT II, except in the context of exploratory therapeutic trials.”
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