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 ctDNA testing as an additional method to identify mCRPC patients with HRR gene alterations who may be eligible for olaparib treatment.
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.
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 to the Cohort A 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]).
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Nov 01 [Epub ahead of print]
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 Harrington, Maha Hussain
National Cancer Center Hospital East, Chiba, Japan., Institute of Cancer Research, Sutton, United Kingdom., Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Madrid, Spain., Fondazione IRCCS Istituto nazionale Tumori, Milan, Italy., Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan., Ankara University, Ankara, Turkey., Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands., Centre Léon Bérard, Lyon, France., Johns Hopkins University, Baltimore, MD, United States., Yonsei University College of Medicine, Seoul, Korea (South), Republic of., Hamilton Health Sciences, Hamilton, Ontario, Canada., Hospital Britanico de Buenos Aires, Buenos Aires, Argentina., Medical University of Vienna, Vienna, Austria., University of Utah/Huntsman Cancer Institute, Salt lake City, UT, United States., British Columbia Cancer Agency, Vancouver, British Columbia, Canada., AstraZeneca Pharmaceuticals, Cambridgeshire, United Kingdom., AstraZeneca (United Kingdom), Cambridge, United Kingdom., AstraZeneca (United States), Gaithersburg, United States., Merck & Co, Inc., Kenilworth, New Jersey, United States., Northwestern University, Chicago, IL, United States.