Using circulating tumor DNA (ctDNA) testing to predict recurrence and guide therapy in patients with triple-negative breast cancer (TNBC) is challenging due to the rapid nature of relapse, according to researchers.

The team conducted a phase 2 trial to assess the utility of prospective ctDNA surveillance in TNBC and evaluate the activity of pembrolizumab in patients who were positive for ctDNA. The results were published in Annals of Oncology.

The phase 2 study ( Identifier: NCT03145961) included 161 evaluable patients with early-stage TNBC and residual disease after neoadjuvant chemotherapy or stage II-III disease with adjuvant chemotherapy. 

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Blood samples were evaluated at baseline and every 3 months for 1 year for active surveillance of ctDNA, then up to 2 years for retrospective analysis. 

Patients who were positive for ctDNA were randomly assigned 2:1 to an intervention or observation. For the intervention, patients without metastatic recurrence on imaging were offered pembrolizumab. Patients who had metastatic recurrence or declined pembrolizumab were treated with standard care off trial. 

The co-primary endpoints of the study were the rate of ctDNA detection and sustained ctDNA clearance with pembrolizumab.

The ctDNA detection rate was 27.3% by 12 months, which was the expected rate, according to the researchers. Patients with high-risk disease had a higher rate of ctDNA detection than patients with moderate-risk disease — 55.7% and 11.8%, respectively.

Of the patients positive for ctDNA, 45 participated in the therapeutic component of the study, with 31 assigned to the intervention and 14 assigned to observation. The median time from ctDNA detection to disease recurrence was 1.6 months in the intervention group and 4.1 months in the observation group. 

Metastases were present in 71.9% of patients at the time of ctDNA detection. This was “substantially higher than anticipated,” the researchers noted.

There were 9 patients who had ctDNA but no metastatic disease. In this group, 5 patients received pembrolizumab and 4 declined the treatment. Of the 4 patients who declined pembrolizumab, 2 ultimately relapsed, and 2 withdrew from the study. 

Of the 5 patients who received pembrolizumab, none achieved ctDNA clearance at 6 months, and all relapsed. In the observation group, 3 of 14 patients (21.4%) achieved ctDNA clearance at 6 months.

The researchers concluded that these findings “have implications for future trial design, emphasizing the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.”

Disclosures: This study was partly supported by Merck Sharp & Dohme Limited. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Turner NC, Swift C, Jenkins B, et al. 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. Ann Oncol. Published online November 21, 2022. doi:10.1016/j.annonc.2022.11.005