The neoadjuvant combination of paclitaxel, trastuzumab, and pertuzumab (THP) shows promise for treating early-stage ERBB2-positive breast cancer. However, evidence on THP’s long-term outcomes is limited, and the role of ultrasensitive circulating tumor DNA (ctDNA) monitoring remains uncertain.
In a prespecified secondary analysis of the phase 2 DAPHNe clinical trial, published in JAMA Oncology, Paolo Tarantino, MD, PhD, and colleagues evaluated the 5-year outcomes of neoadjuvant THP for patients with ERBB2-positive breast cancer. They also assessed the ctDNA dynamics to determine whether ctDNA monitoring can provide a complementary measure of treatment response.
Participants (n=98) included those with stage II to III ERBB2-positive breast cancer receiving neoadjuvant THP for 12 weeks. Ultrasensitive ctDNA analyses were performed for the 57 participants who had available tumor tissue and serial plasma samples.
The main outcomes included 5-year event-free survival, recurrence-free interval (RFI), distant RFI, and overall survival. Results showed that with a median follow-up of 5.2 years (interquartile range, 5.0-5.4 years), the 5-year event-free survival was 99% (95% CI, 97%-100%), the 5-year RFI was 98% (95% CI, 93%-100%), the 5-year distant RFI was 100% (95% CI, 100%-100%), and the 5-year overall survival was 99% (95% CI, 97%-100%).
The researchers also used a whole-genome–based, tumor-informed ultrasensitive assay to assess ctDNA detection and clearance. At baseline, ctDNA was detected in 89.5% of patients (n=51), but ctDNA clearance occurred in 96.1% of these patients (n=49) after neoadjuvant therapy. Detectability remained low (<10%) during postoperative follow-up. Only one patient experienced a local recurrence, and ctDNA cleared after surgical resection.
Overall, the researchers conclude that neoadjuvant THP was associated with excellent long-term outcomes for patients with early-stage ERBB2-positive breast cancer, with near-universal ctDNA clearance. However, they add that, because the sample size in this study was small, further research in larger cohorts is still needed to validate ctDNA as a prognostic biomarker in this setting.