Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA.
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Date
2023-01-04ICR Author
Author
Matsubara, N
de Bono, J
Olmos, D
Procopio, G
Kawakami, S
Ürün, Y
van Alphen, R
Flechon, A
Carducci, MA
Choi, YD
Hotte, SJ
Korbenfeld, E
Kramer, G
Agarwal, N
Chi, KN
Dearden, S
Gresty, C
Kang, J
Poehlein, C
Harrington, EA
Hussain, M
Type
Journal Article
Metadata
Show full item recordAbstract
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 ATM alterations in ctDNA. Only patients from Cohort A (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.
Collections
Research team
PrCa Targeted Therapy
Language
eng
Date accepted
2022-10-28
License start date
2022-11-01
Citation
Clinical Cancer Research, 2022, pp. CCR-21-3577 -
Publisher
AMER ASSOC CANCER RESEARCH