Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Journal

Nature medicine

ISSN: 1546-170X

Titre abrégé: Nat Med

Pays: United States

ID NLM: 9502015

Informations de publication

Date de publication:
14 Sep 2024

Historique:

received: 07 08 2024

accepted: 23 08 2024

medline: 15 9 2024

pubmed: 15 9 2024

entrez: 14 9 2024

Statut: aheadofprint

Résumé

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2

Identifiants

DOI: 10.1038/s41591-024-03266-2 PMID: 39277671

pubmed: 39277671

doi: 10.1038/s41591-024-03266-2

pii: 10.1038/s41591-024-03266-2

doi:

Banques de données

ClinicalTrials.gov

['NCT01042379']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)

ID : P01CA210961

Informations de copyright

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