Abstract P4-01-28: The role of ctDNA clearance in the adjuvant setting in triple negative breast cancer patients with residual tumors after neoadjuvant chemotherapy in the TRICIA trial

Abstract Triple negative breast cancer patients with incomplete response to neoadjuvant chemotherapy (NAC) have a poor prognosis. The CREATE-X clinical trial showed that the addition of adjuvant capecitabine resulted in a 42% decrease in disease relapse (Hazard Ratio 0.58). The TRICIA trial is a multicentre trial for TNBC patients with residual disease after NAC, in which plasma was collected after NAC pre-operatively (T1), immediately after surgery (T2, median 1.1 months), 3 months (T3, median 3.8 months) and at least 6 months after surgery (T4, median 8.7 months). The median follow up of these patients is 32 months. We assayed for circulating tumor DNA (ctDNA) in these samples using a tumor-informed academic digital droplet PCR approach (Cavallone L et al, Sci Reports 2019). We recently reported that the lack of ctDNAdetection in plasma collected at the post-NAC pre-operative timepoint is highly prognostic with 95% of patients with undetectable ctDNA at this T1 time point not presenting distant disease relapse. We now focus on the ctDNA clearance during the post-surgical period in 42 patients who had detectable ctDNA after surgery (T2) and a blood collection at T4. 32 of these patients received capecitabine while 10 did not (before the CREATE-X report). This is the largest series of TNBC patients with residual disease at surgery with serial ctDNA measurements before (T2), during (T3) and immediately after capecitabine treatment (T4). In the 10 non-capecitabine patients, only 1 cleared and that patient did not show relapse. Of 32 patients receiving adjuvant capecitabine, 13 cleared their ctDNA by the T4 time point (42%, similar to the benefit of capecitabine in the CREATE-X study), significantly higher than in the cohort without capecitabine (p=0.03). Only one of these patients (8%) showed disease relapse. This patient had detectable ctDNA 8 months after T4 and relapsed 33 months after surgery. Four of these 13 with ctDNA clearance had become negative by the T3 time point, while the remainder still had detectable ctDNA at the T3 time point. The relapse-free survival for patients on capecitabine who cleared their ctDNA at T4 was 86% while that for those who did not was 55%, with a HR of 0.16 (95% CI 0.04-.66, p=0.05). These results show that ctDNA clearance in the short-term post-operative period has prognostic value and that the addition of capecitabine increases ctDNA clearance throughout the immediate adjuvant period. The clearance of ctDNA after surgery in these high-risk TNBC patients may be predictive of response to adjuvant capecitabine. Citation Format: Mark Basik, Adriana Aguilar-Mahecha, Talia Roseshter, Anna Klemantovich, Luca Cavallone, Josiane Lafleur, Cathy Lan, Jean Francois Boileau, Manuela Pelmus, Rosanna Pezo, Muriel Brackstone, Terry Ng, Suzan McNamara. The role of ctDNA clearance in the adjuvant setting in triple negative breast cancer patients with residual tumors after neoadjuvant chemotherapy in the TRICIA trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-01-28.