Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA

Nobuaki Matsubara, Johann de Bono, David Olmos, Giuseppe Procopio, Satoru Kawakami, Yüksel Ürün, Robbert van Alphen, Aude Flechon, Michael A. Carducci, Young Deuk Choi, Sebastien J. Hotte, Ernesto Korbenfeld, Gero Kramer, Neeraj Agarwal, Kim N. Chi, Simon Dearden, Christopher Gresty, Jinyu Kang, Christian Poehlein, Elizabeth A. HarringtonMaha Hussain

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Purpose: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment. Patients and Methods: Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test for BRCA1, BRCA2 (BRCA), and ATMalterationsinctDNA.OnlypatientsfromCohortA(BRCA/ATM alteration positive by tissue testing) were evaluated. We compared clinical outcomes, including radiographic progression-free survival (rPFS) between the ctDNA subgroup and Cohort A. Results: Of the 181 (73.9%) Cohort A patients who gave consent for plasma sample ctDNA testing, 139 (76.8%) yielded a result and BRCA/ATM alterations were identified in 111 (79.9%). Of these, 73 patients received olaparib and 38 received control. Patients’ baseline demographics and characteristics, and the prevalence of HRR alterations were comparable with the Cohort A intention-to-treat (ITT) population. rPFS was longer in the olaparib group versus control [median 7.4 vs. 3.5 months; hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.21–0.53; nominal P < 0.0001], which is consistent with Cohort A ITT population (HR, 0.34; 95% CI, 0.25–0.47). Conclusions: When tumor tissue testing is not feasible or has failed, ctDNA testing may be a suitable alternative to identify patients with mCRPC carrying BRCA/ATM alterations who may benefit from olaparib treatment.

Original languageEnglish
Pages (from-to)92-99
Number of pages8
JournalClinical Cancer Research
Volume29
Issue number1
DOIs
Publication statusPublished - 2023 Jan 1

Bibliographical note

Publisher Copyright:
©2022 The Authors; Published by the American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • General Medicine

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