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After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.
In BRE12-158 ctDNA detected after neoadjuvant chemotherapy carried a distant disease-free survival hazard ratio of 2.99 and an overall survival hazard ratio of 4.16, and two-year distant disease-free survival was 56 versus 81 percent. c-TRAK TN tracked one or two mutations by digital PCR every three months: 27 percent turned positive within a year but 72 percent of those already had metastases and none of five given pembrolizumab cleared. The residual disease trials now running (ASCENT-05, TROPION-Breast03) enrol on residual cancer burden alone and treat everyone; the residual cancer burden pooled analysis shows RCB-I patients have ten-year relapse-free survival of 81 percent and may be over-treated, while RCB-III patients relapse in three quarters of cases and may need more than one agent. Tumour-informed assays and a first sample at surgery are the design changes c-TRAK TN's authors called for.
The first prospective test of acting on ctDNA in triple-negative disease, and a negative one: with a quarterly, single-mutation assay the window between detectable DNA and visible metastasis was too short to intervene. Later designs use tumour-informed assays, earlier sampling and drugs with more single-agent activity.
The external validation the 2017 paper asked for; it is why residual cancer burden is reported in UK and European pathology and used as a trial entry criterion rather than an MD Anderson curiosity.
The proof that a blood test can split residual-disease patients into those likely to relapse and those likely cured, the premise of the ctDNA-guided adjuvant idea; no completed trial has yet acted on the result.
Turned residual disease from yes or no into a graded score; RCB II and III are now the entry criteria for post-neoadjuvant trials (ASCENT-05, TROPION-Breast03) and the population the ctDNA-guided idea targets.
Established that residual disease after neoadjuvant chemotherapy is a treatable state, the principle behind OlympiA and the post-neoadjuvant antibody-drug conjugate trials; capecitabine remains the option for residual triple-negative disease without a BRCA variant in ESMO, NCCN and UK practice.
Shares Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy, Residual cancer burden (RCB), Neoadjuvant / adjuvant / perioperative, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares Datopotamab deruxtecan, Sacituzumab govitecan, Trial design, endpoints and cost, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares KEYNOTE-522, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares KEYNOTE-522, Neoadjuvant / adjuvant / perioperative, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Datopotamab deruxtecan, Sacituzumab govitecan, Trial design, endpoints and cost, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares KEYNOTE-522, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares KEYNOTE-522, Trial design, endpoints and cost, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab and the tag tnbc-evidence.
Shares KEYNOTE-522, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.