BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma patients

Abstract : BACKGROUND : This study aimed to determine whether the BRCA1 haplotype was associated with trabectedin efficacy in soft-tissue sarcoma (STS) patients. METHODS : We analysed BRCA1 single-nucleotide polymorphisms (SNPs) in tumour specimens from 135 advanced STS patients enrolled in published phase 2 trials or in a compassionate-use programme of trabectedin. Forty-four advanced STS patients treated with doxorubicin and 85 patients with localised STS served as controls. The 6-month nonprogression rate and overall survival (OS) were analysed according to BRCA1 haplotype using log-rank tests. RESULTS : A favourable BRCA1 haplotype (presence of at least one AAAG allele) was significantly associated with an improved 6-month nonprogression rate. It was the only variable significantly associated with OS. No correlations were found between outcomes for patients with localised or advanced STS treated with doxorubicin. CONCLUSIONS : The BRCA1 haplotype represents a potential DNA repair biomarker that can be used for the prediction of response to trabectedin in STS patients.
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Soumis le : mardi 3 septembre 2019 - 15:55:12
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A Laroche-Clary, V Chaire, V Le Morvan, A. Neuville, F. Bertucci, et al.. BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma patients. British Journal of Cancer, Cancer Research UK, 2015, 112 (4), pp.688-692. ⟨10.1038/bjc.2014.624⟩. ⟨hal-02277467⟩



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