ctDNA accurately identifies breast cancer targeted therapy candidates
medwireNews: Testing for circulating tumor (ct)DNA accurately identifies patients with breast cancer suitable for mutation-targeted therapies, results of the phase 2a plasmaMATCH trial show.
Writing in The Lancet Oncology, Nicholas Turner (Institute of Cancer Research, London, UK) and co-authors say: “Patients with rare, potentially targetable mutations in HER2 and AKT1 in ctDNA had clinically important responses with the HER2 inhibitor neratinib and AKT inhibitor capivasertib, respectively.”
They believe their findings “confirm that these mutations are targetable for breast cancer therapy, and demonstrate the validity and clinical utility of using ctDNA testing to screen patients for rare mutations.”
The study included 1034 women who had received at least one previous line of treatment for advanced breast cancer or had relapsed within 12 months of neoadjuvant or adjuvant chemotherapy.
The researchers report that there was a high level of agreement between different ctDNA testing techniques (96–99%), and also high sensitivity for ctDNA digital PCR when compared with mutations identified in advanced breast cancer tissue biopsies, at 93% overall and 98% with concurrent biopsies.
They further analyzed the outcomes among four cohorts of patients with rare targetable mutations who were given targeted therapies matched to the respective mutations without confirmatory tumor testing.
During a median 14.4 months of follow-up, 25% of 20 patients with HER2 mutations treated with oral neratinib 240 mg with or without standard-dose fulvestrant had an objective response, with a median response duration of 5.7 months and a median progression-free survival (PFS) of 5.4 months.
The response rate was 22% among the 18 patients with AKT1 mutations and estrogen receptor (ER)-positive cancer treated with oral capivasertib 400 mg plus fulvestrant, 11% among the 19 patients with AKT1 mutations and ER-negative cancer or a PTEN mutation treated with oral capivasertib 480 mg, and 8% among the 74 patients with ESR1 mutations treated with intramuscular extended-dose fulvestrant 500 mg.
The median response durations in these three groups were 7.5, 3.9, and 7.0 months, respectively, while median PFS was 10.2, 3.4, and 2.2 months, respectively.
The researchers say that the treatment responses were “comparable to previous studies involving tumour tissue testing,” but note that only the individuals with HER2 reached the predefined target response rate of 25%, with patients in the AKT1, ER-positive cohort falling just short of this target.
Turner et al conclude that “ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice.”
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