Genomics to select treatment for patients with metastatic breast cancer.
Nature
; 610(7931): 343-348, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-36071165
ABSTRACT
Cancer progression is driven in part by genomic alterations1. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations2, leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment5 with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)6 (adjusted hazards ratio (HR) 0.41, 90% confidence interval (CI) 0.27-0.61, P < 0.001), but not when alterations are unselected using ESCAT (adjusted HR 0.77, 95% CI 0.56-1.06, P = 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR 1.15, 95% CI 0.76-1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2 mutations (n = 49) derived high benefit from olaparib (gBRCA1 HR = 0.36, 90% CI 0.14-0.89; gBRCA2 HR = 0.37, 90% CI 0.17-0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Genoma Humano
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Genômica
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Tomada de Decisão Clínica
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Metástase Neoplásica
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article