De-escalated Paclitaxel, Trastuzumab, and Pertuzumab Yield Excellent Long-Term Outcomes in HER2-Positive Breast Cancer
Clinical Summary:
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Design/Population: This prespecified secondary analysis of the phase 2 DAPHNe trial evaluated 5-year clinical outcomes and ultrasensitive circulating tumor DNA (ctDNA) dynamics in patients with stage II to III HER2-positive breast cancer treated with abbreviated neoadjuvant paclitaxel, trastuzumab, and pertuzumab.
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Key Outcomes: De-escalated paclitaxel, trastuzumab, and pertuzumab produced excellent long-term outcomes, with 5-year event-free survival and overall survival rates of 99%. Ultrasensitive ctDNA was detected in most patients at baseline and cleared in nearly all evaluable patients following neoadjuvant therapy.
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Clinical Relevance: These findings support abbreviated paclitaxel, trastuzumab, and pertuzumab as an effective neoadjuvant de-escalation strategy for selected patients with HER2-positive breast cancer and support further investigation of ultrasensitive ctDNA as a biomarker for treatment monitoring and future de-escalation approaches.
Results from a prespecified secondary analysis of the phase 2 DAPHNe trial demonstrated that abbreviated neoadjuvant paclitaxel, trastuzumab, and pertuzumab produced excellent long-term outcomes in patients with stage II to III HER2-positive breast cancer, while ultrasensitive circulating tumor DNA (ctDNA) analysis demonstrated near-universal ctDNA clearance following treatment.
“The neoadjuvant combination of paclitaxel, trastuzumab, and pertuzumab represents a promising abbreviated regimen for early-stage [HER2]-positive breast cancer, but long-term outcomes and the role of ultrasensitive [ctDNA] monitoring remain incompletely defined,” stated Paolo Tarantino, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors.
In this phase trial, 98 patients received neoadjuvant paclitaxel, trastuzumab, and pertuzumab for 12 weeks followed by surgery and response-guided adjuvant therapy. A subset of 57 patients with available tumor tissue and serial plasma samples underwent ultrasensitive tumor-informed ctDNA analysis. End points for this secondary analysis included 5-year event-free survival (EFS), recurrence-free interval, distant recurrence-free interval, overall survival (OS), and ctDNA dynamics.
After a median follow-up of 5.2 years, the 5-year EFS rate was 99%, the recurrence-free interval was 98%, the distant recurrence-free interval was 100%, and the 5-year OS rate was 99%. Only 1 local recurrence occurred during follow-up, and no distant recurrences were observed.
Among patients included in the ctDNA analysis, ctDNA was detected at baseline in 89.5% of patients. Following neoadjuvant therapy, ctDNA clearance occurred in 96.1% of patients with detectable baseline ctDNA, with only 2 patients remaining ctDNA-positive before surgery. During postoperative surveillance, ctDNA detected the single local recurrence before becoming undetectable after surgical resection.
No significant association was observed between ctDNA clearance and pathologic complete response. However, the high baseline ctDNA detection rate and near-universal clearance after treatment support further investigation of ultrasensitive ctDNA as a biomarker for treatment monitoring and future response-adapted treatment strategies.
“De-escalated [paclitaxel plus trastuzumab and pertuzumab] produced excellent long-term outcomes, and near-universal ultrasensitive ctDNA clearance after treatment, warranting further validation of ultrasensitive ctDNA as a prognostic tool in this setting,” concluded Dr Tarantino et al.
Source:
Tarantino P, Li T, Ogayo ER, et al. Neoadjuvant paclitaxel, trastuzumab, and pertuzumab for stage II to III, ERBB2-positive breast cancer. JAMA Oncol. Published online: June 25, 2026. doi: 10.1001/jamaoncol.2026.2023
