SAN ANTONIO – The high accuracy and efficiency of circulating tumor DNA (ctDNA) testing allows for routine clinical use in advanced breast cancer, according to investigators.
The plasmaMATCH trial showed that gene level agreement between ctDNA results measured by digital PCR versus sequencing was as high as 99.4%, reported lead author Nicholas Turner, MA, MRCP, PhD, of The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London.
Dr. Turner, who presented findings at the San Antonio Breast Cancer Symposium, said that ctDNA testing can detect rare mutations and link patients with targeted therapies that have clinically relevant response rates.
“Multiple somatic mutations are potentially targetable in the treatment of advanced breast cancer,” Dr. Turner said. “In addition, mutations may be acquired [during treatment].”
The diverse and dynamic landscape of mutations in breast cancer creates a need to genotype tumors without repeating biopsies, Dr. Turner said. He noted that ctDNA is one possible means of fulfilling this need, although more prospective research is required to determine clinical utility.
To this end, the investigators conducted the phase II plasmaMATCH trial, a multiple parallel cohort, multicenter study involving 1,044 patients with advanced breast cancer. All patients had ctDNA testing performed prospectively with digital droplet PCR (ddPCR); in addition, ctDNA testing was performed with error-corrected sequencing using Guardant360, either prospectively or retrospectively. If actionable mutations were identified, and consent was provided, then patients entered the treatment cohort, which was composed of 142 participants.
Patients were divided into four parallel treatment cohorts based on ctDNA mutation results and accompanying treatments, as follows:
- (A) ESR1 mutation; extended-dose fulvestrant.
- (B) HER2 mutation; neratinib with or without fulvestrant.
- (C) AKT1 in estrogen receptor–positive disease; capivasertib plus fulvestrant.
- (D) “AKT basket” – AKT1 in estrogen receptor–negative disease or PTEN inactivating mutation; capivasertib.
The primary objective was response rate. For cohort A, at least 13 out of 78 evaluable patients (17%) needed to have a response to infer sufficient efficacy of the matched therapy. For the remaining cohorts, sufficient efficacy was defined by responses in at least 3 out of 16 evaluable patients (19%).