[en] PARP inhibitors, such as rucaparib, have been well characterized in metastatic castration-resistant prostate cancer (mCRPC) associated with BRCA alterations, and the clinical activity of these agents has also been evaluated in patients with mCRPC associated with alterations in other non-BRCA DNA damage repair (DDR) genes, including RAD51B. There is likely a differential sensitivity to PARP inhibition based on the specific DDR gene altered, but research in this area is limited because of the low frequency of alterations in these genes. Here, we describe a mCRPC patient with a truncating rearrangement of RAD51B who had a radiographic and PSA response when treated with the PARP inhibitor rucaparib within the TRITON2 trial. We investigated the patients' response parameters, circulating tumor DNA (ctDNA) fraction and tumor genomics longitudinally, using next-generation sequencing (NGS) of tissue and plasma. ctDNA fraction correlates with radiographic and PSA response and is lower during times of response. NGS did not reveal any potential genomic mechanism of acquired drug resistance. This case shows evidence for rucaparib activity in a rare patient with mCRPC and a RAD51B truncation.
Disciplines :
Oncology
Author, co-author :
Sautois, Brieuc ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Loehr, Andrea; Translational Medicine, Clovis Oncology Inc., Boulder, CO 08006, USA
Watkins, Simon P ; Clinical Science, Clovis Oncology UK, Ltd., Cambridge CB21 6GP, UK
SCHROEDER, Hélène ; Centre Hospitalier Universitaire de Liège - CHU > > Centre d'oncologie
Abida, Wassim; Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Language :
English
Title :
A Case Study of Clinical Response to Rucaparib in a Patient with Metastatic Castration-Resistant Prostate Cancer and a RAD51B Alteration.
Funding: TRITON2 was funded by Clovis Oncology. W.A. is supported in part by the National Cancer Institute (NCI) Cancer Center Support Grant P30 CA 008748, the NCI Prostate Specialized Program of Research Excellence (SPORE) Grant P50 CA092629-16, the Department of Defense Prostate Cancer Research Program Grant W81XWH-17-1-0124, and a Prostate Cancer Foundation Young Investigator Award.Acknowledgments: Medical writing and editorial support funded by Clovis Oncology, Inc., were provided by Shelly Lim and Stephen Bublitz of Ashfield MedComms, an Ashfield Health company.
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