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BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma patients |
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| Authors: | A Laroche-Clary V Chaire V Le Morvan A Neuville F Bertucci S Salas R Sanfilippo P Pourquier A Italiano |
| Institution: | 1.INSERM U916 and University of Bordeaux, Bordeaux, France;2.Institut Bergonié, Bordeaux, France;3.Institut Paoli Calmettes, Marseille, France;4.Assistance Publique des Hôpitaux de Marseille, Hôpital la Timone, Marseille, France;5.Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Instituto Nazionale Tumori, Milan, Italy |
| 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. |
| Keywords: | sarcoma polymorphism BRCA1 trabectedin predictive biomarkers |