[en] PURPOSE: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA(+)), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA(+) mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. PATIENTS AND METHODS: Patients had progressed after next-generation androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. RESULTS: TRITON2 enrolled 115 patients with BRCA(+) identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA(+) by tissue testing. CONCLUSIONS: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA(+) mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
Disciplines :
Oncology
Author, co-author :
Loehr, Andrea
Patnaik, Akash
Campbell, David
Shapiro, Jeremy
Bryce, Alan H.
McDermott, Ray
Sautois, Brieuc ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol 2020; 38:3763-72.
Stetson D, Ahmed A, Xu X, Nuttall BRB, Lubinski TJ, Johnson JH, et al. Orthogonal comparison of four plasma NGS tests with tumor suggests technical factors are a major source of assay discordance. JCO Precis Oncol 2019; 3:1-9.
Green F, Shapiro JD, McDermott R, Piulats JM, Reid A, Ostler P, et al. Comprehensive genomic profiling of >1000 plasma and tumor tissue samples from metastatic castration-resistant prostate cancer (mCRPC) patients gives insight into targeted treatment strategies. Cancer Res 2019; 79:abstr 727.
Chung JH, Dewal N, Sokol E, Mathew P, Whitehead R, Millis SZ, et al. Prospective comprehensive genomic profiling of primary and metastatic prostate tumors. JCO Precis Oncol 2019; 3:PO.18.00283.
Scher HI, Solo K, Valant J, Todd MB, Mehra M. Prevalence of prostate cancer clinical states and mortality in the United States: Estimates using a dynamic progression model. PLoS One 2015; 10:e0139440.
Scher HI, Heller G. Clinical states in prostate cancer: Toward a dynamicmodel of disease progression. Urology 2000; 55:323-7.
Abida W, Armenia J, Gopalan A, Brennan R, Walsh M, Barron D, et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. JCO Precis Oncol 2017; 1:1-16.
Steinkamp MP, O'Mahony OA, Brogley M, Rehman H, Lapensee EW, Dhanasekaran S, et al. Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res 2009; 69:4434-42.
Mateo J, Seed G, Bertan C, Rescigno P, DollingD, Figueiredo I, et al. Genomics of lethal prostate cancer at diagnosis and castration resistance. J Clin Invest 2020; 130:1743-51.
Schweizer MT, Sivakumar S, Tukachinsky H, Coleman I, De Sarkar N, Yu EY, et al. Concordance of DNA repair gene mutations in paired primary prostate cancer samples andmetastatic tissue or cell-free DNA. JAMA Oncol 2021; 7:1-5.
Wong SK, Mohamad NV, Giaze TR, Chin KY, Mohamed N, Ima-Nirwana S. Prostate cancer and bone metastases: The underlying mechanisms. Int J Mol Sci 2019; 20:2587.
Ross RW, Halabi S, Ou SS, Rajeshkumar BR, Woda BA, Vogelzang NJ, et al. Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer-a Cancer and Leukemia Group B study. Clin Cancer Res 2005; 11:8109-13.
McKay RR, Zukotynski KA, Werner L, Voznesensky O, Wu JS, Smith SE, et al. Imaging, procedural and clinical variables associated with tumor yield on bone biopsy in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 2014; 17:325-31.
Gandaglia G, Abdollah F, Schiffmann J, Trudeau V, Shariat SF, Kim SP, et al. Distribution of metastatic sites in patients with prostate cancer: A populationbased analysis. Prostate 2014; 74:210-6.
Sailer V, Schiffman MH, Kossai M, Cyrta J, Beg S, Sullivan B, et al. Bone biopsy protocol for advanced prostate cancer in the era of precision medicine. Cancer 2018; 124:1008-15.
Lorente D, Omlin A, Zafeiriou Z, Nava-Rodrigues D, Perez-Lopez R, Pezaro C, et al. Castration-resistant prostate cancer tissue acquisition from bone metastases for molecular analyses. Clin Genitourin Cancer 2016; 14:485-93.
Malapelle U, Sirera R, Jantus-Lewintre E, Reclusa P, Calabuig-Farinas S, Blasco A, et al. Profile of the Roche cobas(R) EGFR mutation test v2 for nonsmall cell lung cancer. Expert Rev Mol Diagn 2017; 17:209-15.
Hsiue EH, Lee JH, Lin CC, Yang JC. Profile of the therascreen(R) EGFR RGQ PCR kit as a companion diagnostic for gefitinib in non-small cell lung cancer. Expert Rev Mol Diagn 2016; 16:1251-7.
Satouchi M, Tanaka H, Yoshioka H, Shimokawaji T, Mizuno K, Takeda K, et al. Detection of epidermal growth factor receptor gene T790M mutation in cytology samples using the cobas((R)) EGFR mutation test. Lung Cancer 2017; 111:190-4.
Clark TA, Chung JH, Kennedy M, Hughes JD, Chennagiri N, Lieber DS, et al. Analytical validation of a hybrid capture-based next-generation sequencing clinical assay for genomic profiling of cell-free circulating tumor DNA. J Mol Diagn 2018; 20:686-702.
Oliveira KCS, Ramos IB, Silva JMC, Barra WF, Riggins GJ, Palande V, et al. Current perspectives on circulating tumor DNA, precision medicine, and personalized clinical management of cancer. Mol Cancer Res 2020; 18:517-28.
Husain H, Velculescu VE. Cancer DNA in the circulation: The liquid biopsy. JAMA 2017; 318:1272-4.
Wyatt AW, Azad AA, Volik SV, Annala M, Beja K, McConeghy B, et al. Genomic alterations in cell-free DNA and enzalutamide resistance in castration-resistant prostate cancer. JAMA Oncol 2016; 2:1598-606.
Volik S, Alcaide M, Morin RD, Collins C. Cell-free DNA (cfDNA): Clinical significance and utility in cancer shaped by emerging technologies. Mol Cancer Res 2016; 14:898-908.
Annala M, Fu S, Bacon JVW, Sipola J, Iqbal N, Ferrario C, et al. Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castrationresistant prostate cancer: A multicentre, randomised, open-label, phase II trial. Ann Oncol 2021; 32:896-905.
Maurice-Dror C, Fonseca N, Herberts C, Fan W, Wyatt AW, ChiKN. Circulating tumor DNA fraction (ctDNA%) to independently predict for clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 2021; 39:5049
Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat Commun 2017; 8:1324.
Wyatt AW, Annala M, Aggarwal R, Beja K, Feng F, Youngren J, et al. Concordance of circulating tumor DNA and matched metastatic tissue biopsy in prostate cancer. J Natl Cancer Inst 2017; 109:djx118.
Bowman RL, Busque L, Levine RL. Clonal hematopoiesis and evolution to hematopoietic malignancies. Cell Stem Cell 2018; 22:157-70.
Jensen K, Konnick EQ, Schweizer MT, Sokolova AO, Grivas P, Cheng HH, et al. Association of clonal hematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference. JAMA Oncol 2021; 7:107-10.
Beware liquid biopsies to guide PARP blockade. Cancer Discov 2021; 11:6.
Reichert ZR, Jones MA, Alumkal JJ.A CHIP in the armor of cell-free DNA-based predictive biomarkers for prostate cancer. JAMA Oncol 2021; 7:111-2.
Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013; 31:1023-31.
Crawford B, Adams SB, Sittler T, van den Akker J, Chan S, Leitner O, et al. Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients. Breast Cancer Res Treat 2017; 163:383-90.
Cheng DT, Mitchell TN, Zehir A, Shah RH, Benayed R, Syed A, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): A hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn 2015; 17:251-64.
Reid R, DiGiovanni M, Bernhisel R, Brown K, Saam J, Lancaster J. Inherited germlinemutations inmen with prostate cancer. J Clin Oncol 2018; 36(suppl 6S): Abstr 357.
Pritzlaff M, Tian Y, Reineke P, Stuenkel AJ, Allen K, Gutierrez S, et al. Diagnosing hereditary cancer predisposition in men with prostate cancer. Genet Med 2020; 22:1517-23.
Abida W, Campbell D, Patnaik A, Sautois B, Shapiro J, Vogelzang N, et al. Genomic characteristics associated with clinical activity of rucaparib in patients (pts) with BRCA1 or BRCA2 (BRCA)-mutated metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 2020; 38:abstr178.
FoundationOne_ Liquid CDx. Technical Specifications. Foundation Medicine, Inc; 2020. [cited 2020 Sept 22]. Available from: https://assets. ctfassets.net/w98cd481qyp0/wVEm7VtICYR0sT5C1VbU7/cc6ac2109785d70 fe6d91903b241006f/FoundationOne_Liquid_CDx_Technical_Specifications. pdf.