plasmaMATCH
plasmaMATCH showed that a blood test can find the mutations that steer treatment in advanced breast cancer as reliably as a tumour biopsy, and used it to send women straight to drugs matching rare mutations. It found real activity for neratinib in HER2-mutant and capivasertib in AKT1-mutant disease.
Overview
plasmaMATCH was led by Nicholas Turner at the Institute of Cancer Research and the Royal Marsden and opened in December 2016 at hospitals across the United Kingdom. More than a thousand women with advanced breast cancer had circulating tumour DNA sequenced (with Guardant360 and digital PCR); those with a qualifying mutation entered one of four treatment cohorts: A, ESR1 mutations, extended-dose fulvestrant; B, HER2 mutations, neratinib with or without fulvestrant; C, AKT1 mutations in oestrogen receptor-positive disease, capivasertib with fulvestrant; D, AKT1 mutations in receptor-negative disease or PTEN loss, capivasertib alone. A fifth cohort, E, later gave olaparib with the ATR inhibitor ceralasertib to triple-negative disease.
The Lancet Oncology report in 2020 established the diagnostic claim: circulating tumour DNA testing agreed with tissue sequencing in the great majority of patients, with sensitivity around 93 percent, so a blood test could stand in for a biopsy to select therapy. On the therapeutic side, neratinib in HER2-mutant cancer and capivasertib with fulvestrant in AKT1-mutant receptor-positive cancer met their pre-set response thresholds (about a quarter and a fifth of patients responding), capivasertib alone in cohort D showed less activity, and extended-dose fulvestrant for ESR1 mutations did not meet its bar. Cohort E, in Clinical Cancer Research in 2023, found limited activity for olaparib with ceralasertib in unselected triple-negative disease. A 2026 analysis showed that the amount of circulating tumour DNA predicted survival across the cohorts.
plasmaMATCH changed United Kingdom practice by validating plasma-first genotyping in advanced breast cancer, contributed the largest neratinib series in HER2-mutant breast cancer alongside SUMMIT, and supplied part of the rationale for capivasertib's development in AKT pathway-altered disease that led to its approval with fulvestrant in 2023. It also modelled a national umbrella run from a blood test, a design DETERMINE and TARGET National inherited.
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