Abstract OT1-06-03: The plasmaMATCH trial: A multiple parallel cohort, open-label, multi-centre phase II clinical trial of ctDNA screening to direct targeted therapies in patients with advanced breast cancer (CRUK/15/010)
Authors: N Turner, H Bye, S Kernaghan, P Proszek, C Fribbens, L Moretti, J Morden, C Snowdon, I Macpherson, A Wardley, R Roylance, R Baird, J Bliss, A Ring
Journal: Cancer Research (2018)

Abstract Introduction Circulating tumour DNA (ctDNA) is found in the plasma of over 90% of patients with advanced breast cancer (BC). Screening for the presence of mutations in ctDNA provides a current assessment of the genetic profile of the patient's recurrent BC. The plasmaMATCH trial is designed to assess the potential of ctDNA screening to direct targeted therapies in patients with advanced breast cancer. Methods plasmaMATCH is a multi-centre phase IIa umbrella trial platform of ctDNA screening and a therapeutic trial. The study will screen 1000 women with advanced breast cancer, who have received prior systemic treatment in the advanced setting, with digital PCR ctDNA assays for hotspot mutations in ESR1, HER2, AKT1, and PIK3CA, with HER2 copy number assessment, in a central laboratory. The study will recruit from up to 50 sites in the UK. Patients with mutations identified will enter the matching treatment cohort, ESR1 – extended dose fulvestrant 500mg every two weeks, HER2 – neratinib +/- fulvestrant, AKT1 – AZD5363 +/- fulvestrant. Mutation prevalence is presented with corresponding exact 95% confidence intervals (CIs) both overall and excluding 14 patients who were known to have mutations from a prior screening program. Patients with more than one mutation are included once in each relevant row. Results We report the results of prospective ctDNA mutation testing in the first 92 patients. plasmaMATCH opened to recruitment on 15/12/2016. As of 08/06/2017, 120 patients have been registered for ctDNA screening from 7 UK centres, of which 92 have ctDNA screening results available: plasmaMATCH ctDNA screening resultsMutationPrevalence (95% CI)Prevalence excluding 14 patients with known mutations (95% CI)ESR134/92: 37% (27%-48%)26/78: 33% (23%-45%)HER25/90: 6% (2%-12%)2/76: 3% (0%-9%)AKT17/92: 8% (3%-15%)4/78: 5% (1%-13%)PIK3CA*22/92: 24% (16%-34%)21/78: 27% (18%-38%)*No corresponding plasmaMATCH treatment cohort 14 patients had more than one mutation detected (10 ESR1+PIK3CA, 3 ESR1+AKT1, 1 ESR1+ +HER2+AKT1). ctDNA results were reported in a median of 8 working days. Of the 40 patients with one or more actionable mutation, 15 have entered a cohort, 16 are being screened for entry into a cohort, 5 are currently receiving further systemic treatment prior to cohort entry and 4 will not enter a cohort. One additional patient has entered a treatment cohort on the basis of a mutation detected in an alternative tumour sequencing initiative. Conclusions plasmaMATCH ctDNA demonstrates the feasibility and accuracy of ctDNA testing as a screening tool for patients with advanced BC, with a high rate of subsequent recruitment into matching therapeutic trials. Citation Format: Turner N, Bye H, Kernaghan S, Proszek P, Fribbens C, Moretti L, Morden J, Snowdon C, Macpherson I, Wardley A, Roylance R, Baird R, Bliss J, Ring A. The plasmaMATCH trial: A multiple parallel cohort, open-label, multi-centre phase II clinical trial of ctDNA screening to direct targeted therapies in patients with advanced breast cancer (CRUK/15/010) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-03.