dc.contributor.author | Turner, NC | |
dc.contributor.author | Swift, C | |
dc.contributor.author | Jenkins, B | |
dc.contributor.author | Kilburn, L | |
dc.contributor.author | Coakley, M | |
dc.contributor.author | Beaney, M | |
dc.contributor.author | Fox, L | |
dc.contributor.author | Goddard, K | |
dc.contributor.author | Garcia-Murillas, I | |
dc.contributor.author | Proszek, P | |
dc.contributor.author | Hall, P | |
dc.contributor.author | Harper-Wynne, C | |
dc.contributor.author | Hickish, T | |
dc.contributor.author | Kernaghan, S | |
dc.contributor.author | Macpherson, IR | |
dc.contributor.author | Okines, AFC | |
dc.contributor.author | Palmieri, C | |
dc.contributor.author | Perry, S | |
dc.contributor.author | Randle, K | |
dc.contributor.author | Snowdon, C | |
dc.contributor.author | Stobart, H | |
dc.contributor.author | Wardley, AM | |
dc.contributor.author | Wheatley, D | |
dc.contributor.author | Waters, S | |
dc.contributor.author | Winter, MC | |
dc.contributor.author | Hubank, M | |
dc.contributor.author | Allen, SD | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | c-TRAK TN investigators, | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-11-28T14:24:33Z | |
dc.date.available | 2022-11-28T14:24:33Z | |
dc.date.issued | 2022-11-21 | |
dc.identifier | S0923-7534(22)04735-4 | |
dc.identifier.citation | Annals of Oncology, 2022, pp. S0923-7534(22)04735-4 - | |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5580 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.doi | 10.1016/j.annonc.2022.11.005 | |
dc.description.abstract | BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes. | |
dc.format | Print-Electronic | |
dc.format.extent | S0923-7534(22)04735-4 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | Annals of Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Breast cancer | |
dc.subject | ctDNA | |
dc.subject | molecular residual disease | |
dc.subject | pembrolizumab | |
dc.title | Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-11-08 | |
dc.date.updated | 2022-11-28T14:23:19Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1016/j.annonc.2022.11.005 | |
rioxxterms.licenseref.startdate | 2022-11-21 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36423745 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.annonc.2022.11.005 | |
icr.researchteam | Clin Trials & Stats Unit | |
dc.contributor.icrauthor | Turner, Nicholas | |
dc.contributor.icrauthor | Kilburn, Lucy | |
dc.contributor.icrauthor | Fox, Lisa | |
dc.contributor.icrauthor | Garcia-Murillas, Isaac | |
dc.contributor.icrauthor | Snowdon, Claire | |
dc.contributor.icrauthor | Bliss, Judith | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Judith Bliss) on 2022-11-28. Deposit type is initial. No. of files: 1. Files: PIIS0923753422047354.pdf | |