Homologous Recombination Repair Gene Mutation Characterization by Liquid Biopsy: A Phase II Trial of Olaparib and Abiraterone in Metastatic Castrate-Resistant Prostate Cancer.
Fiche publication
Date publication
novembre 2021
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr THIERY-VUILLEMIN Antoine
Tous les auteurs :
Carr TH, Adelman C, Barnicle A, Kozarewa I, Luke S, Lai Z, Hollis S, Dougherty B, Harrington EA, Kang J, Saad F, Sala N, Thiery-Vuillemin A, Clarke NW, Hodgson D, Barrett JC
Lien Pubmed
Résumé
Phase III randomized trial data have confirmed the activity for olaparib in homologous recombination repair (HRR) mutated metastatic castration-resistant prostate cancer (mCRPC) post next-generation hormonal agent (NHA) progression. Preclinical data have suggested the potential for a combined effect between olaparib and NHAs irrespective of whether an HRR gene alteration was present. NCT01972217 was a randomised double-blind Phase II study which evaluated olaparib and abiraterone versus placebo and abiraterone in mCRPC patients who had received prior chemotherapy containing docetaxel. The study showed that radiologic progression was significantly delayed by the combination of olaparib and abiraterone regardless of homologous recombination repair mutation (HRRm) status. The study utilized tumour, blood (germline), and circulating tumour DNA (ctDNA) analysis to profile patient HRRm status, but tumour tissue provision was not mandated, leading to relatively low tissue acquisition and DNA sequencing success rates not representative of real-world testing.
Mots clés
PARP inhibition, circulating tumour DNA (ctDNA), homologous recombination repair (HRR), metastasis, next-generation sequencing (NGS), prostate cancer
Référence
Cancers (Basel). 2021 Nov 20;13(22):