Prevalence and dynamics of circulating tumor DNA (ctDNA) among patients (pts) with HER2+ breast cancer (BC) receiving neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in the DAPHNe trial.
Authors: Adrienne Gropper Waks, Paolo Tarantino, Tianyu Li, Esther R. Ogayo, Tasnim Rahman, Molly DiLullo, Sherif Mohamed El-Refai, Charles Abbott, Sean Michael Boyle, Richard Chen, Neelam Vijay Desai, Laura Spring, Nadine M. Tung, Tari A. King, Ian E. Krop, Nabihah Tayob, Elizabeth A. Mittendorf, Sara M. Tolaney, Eric P. Winer, Heather Anne Parsons
Journal: Journal of Clinical Oncology (2024)

588 Background: Neoadjuvant THP may become a new standard for pts with early stage HER2+ BC pending results of large ongoing trials. Although ctDNA persistence in the (neo)adjuvant setting is associated with elevated risk of distant recurrence, the prevalence and dynamics of ctDNA in HER2+ BC are unknown. Methods: On the single-arm phase II DAPHNe trial, pts with stage II-III HER2+ BC received 12 weeks of neoadjuvant THP, followed by surgery and adjuvant systemic therapy (tx) per physicians’ discretion (with no further chemotherapy in case of pCR). Plasma samples were prospectively collected at 4 timepoints: baseline (BL), pre-operatively (pre-op), immediate post-operatively (post-op), and during the final 3 mos of adjuvant HER2-directed tx. ctDNA was measured using NeXT Personal, a tumor-informed assay based on whole-genome sequencing of tumor/normal samples to detect and quantify minimal residual disease (MRD). We assessed the association of MRD with residual cancer burden (RCB) and long-term outcomes. Results: Of 98 pts enrolled in DAPHNe, 50 had at least one plasma sample sequenced with NeXT Personal. Of these 50 pts, the median age was 50 yrs, 92% had clinical stage II and 64% had hormone-receptor positive (HR+) tumors. RCB scores were: RCB 0 (33/50 pts, 66%), RCB I (2/50 pts, 4%), RCB II (14/50 pts, 28%), RCB III (1/50 pts, 2%). With 50 mos median follow-up, there have been no breast cancer recurrences. ctDNA was detected (ctDNA+) at BL in 42/49 pts (92%) (median detected level 210 parts per million (PPM), broad detection range of 36,978 down to 3 PPM, and 34% of detected pts had ctDNA level &lt;100 PPM). All pts with T3/T4 tumors or positive nodes had BL ctDNA+, whereas 91% and 85% of pts with T1/T2 or node-negative tumors, respectively, had BL ctDNA+. Most pts cleared MRD after THP. Rates of ctDNA detection at post-BL timepoints were: 2/49 pts (4%) at pre-op; 2/48 pts (4%) at post-op; and 1/34 pts (3%) at late adjuvant times. Statistical comparison of pts who cleared vs did not clear ctDNA during neoadjuvant THP was not possible given the high rate of ctDNA positivity at BL and the high rate of negativity pre-op. Clinical vignettes of the 5 pts with detectable MRD at any post-BL timepoint are shown (Table). MRD data from additional pts will be presented. Conclusions: In this population of moderate risk (mostly stage II) HER2+ BC pts, 92% were ctDNA+ at BL. Neoadjuvant THP was very effective at clearing MRD, regardless of whether there was residual disease in the breast/nodes or not, consistent with the absence of any BC recurrence in the cohort to date. Clinical trial information: NCT03716180 . [Table: see text]