The DAPHNe phase 2 single-arm trial evaluated 5-year outcomes and ultrasensitive ctDNA dynamics in 98 patients with stage II–III ERBB2-positive breast cancer receiving 12 weeks of neoadjuvant paclitaxel, trastuzumab, and pertuzumab (THP), followed by response-guided adjuvant therapy (median follow-up 5.2 years).
At 5 years: event-free survival 99%, recurrence-free interval 98%, distant recurrence-free interval 100%, and overall survival 99%. Among 57 patients with ctDNA data, baseline ctDNA was detected in 89.5% (51/57); after neoadjuvant THP, 96.1% (49/51) cleared ctDNA preoperatively. Only one local recurrence occurred across the cohort.
Single-arm, non-randomized design with no comparator group limits causal inference. ctDNA substudy included only 57 of 98 patients (tissue/plasma availability required), introducing potential selection bias. Predominantly stage II (92.9%) and mostly female (99%) cohort limits generalizability to stage III or male patients.
Abbreviated 12-week neoadjuvant THP shows excellent 5-year outcomes for early-stage HER2-positive breast cancer, supporting its use as a chemotherapy-sparing option. Near-universal ctDNA clearance after therapy suggests ctDNA-guided de-escalation strategies warrant prospective randomized study.
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