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c-TRAK TN, run from the Royal Marsden and the Institute of Cancer Research, was the first trial to use blood tests for tumour DNA to trigger treatment in triple-negative breast cancer. A quarter of patients tested positive within a year, but most of them already had visible metastases on scans, so the test came too late to prevent relapse with pembrolizumab.
c-TRAK TN (NCT03145961) registered 208 patients between January 2018 and December 2019 with early triple-negative breast cancer and residual disease after neoadjuvant chemotherapy or stage II to III disease treated with adjuvant chemotherapy; 185 had tumour sequencing, 171 (92.4 percent) had trackable mutations and 161 entered digital PCR ctDNA surveillance every three months for 12 months (18 if samples were missed during the pandemic). ctDNA-positive patients were randomised 2 to 1 to intervention (staging scans, then pembrolizumab for a year if free of recurrence) or blinded observation; a September 2020 amendment closed the observation group. ctDNA was detected in 27.3 percent by 12 months (44 of 161; 95 percent confidence interval 20.6 to 34.9) and seven patients relapsed without prior ctDNA detection. Of 32 patients allocated to intervention, 72 percent (23) already had metastases on staging and four declined pembrolizumab; of the five who started it, none achieved sustained ctDNA clearance, so the second co-primary endpoint was not met. The trial's lesson, that ctDNA surveillance must start earlier and use more sensitive or frequent assays before it can steer adjuvant treatment, shaped the design of the ctDNA-triggered trials now recruiting.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
208 enrolled.
72 percent of ctDNA-positive patients had metastases at staging and were not eligible
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| ctDNA detection by 12 monthsprimary | Patients under ctDNA surveillance | 161 | 27.3% | - | - | link |
| Sustained ctDNA clearance on pembrolizumabprimary | Pembrolizumab | 5 | 0% | - | - | link |
Shares Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point, Residual cancer burden (RCB), KEYNOTE-522, Early triple-negative breast cancer.
Shares Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point, Residual cancer burden (RCB), KEYNOTE-522, Cancer Research UK.
Shares BRE12-158 (Hoosier Oncology Group), Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point, Residual cancer burden (RCB), KEYNOTE-522.
Shares Residual cancer burden (RCB), The Royal Marsden, Cancer Research UK, Circulating tumour DNA (ctDNA).
Shares Residual cancer burden (RCB), KEYNOTE-522, Early triple-negative breast cancer, Merck & Co. (MSD).
Shares Residual cancer burden (RCB), KEYNOTE-522, Early triple-negative breast cancer, Triple-negative breast cancer trials open today (registry snapshot and UK sites).
Shares Residual cancer burden (RCB), Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing, Early triple-negative breast cancer.
Shares Residual disease after neoadjuvant therapy in triple-negative breast cancer: the decision point, Residual cancer burden (RCB), KEYNOTE-522, Early triple-negative breast cancer.