Long-Term Results Support De-escalated Neoadjuvant Therapy in HER2-Positive Breast Cancer
Clinical Summary:
- Design/Population: The phase 2 DAPHNe trial evaluated 12 weeks of neoadjuvant paclitaxel, trastuzumab, and pertuzumab in patients with stage II or III HER2-positive breast cancer. Patients who achieved a pCR omitted additional adjuvant chemotherapy. Five-year outcomes and ultra-sensitive ctDNA analyses were subsequently assessed.
- Key Outcomes: At 5 years, the recurrence-free interval was 98%, with only 1 local recurrence and no distant recurrences. Nearly all patients converted from ctDNA-positive at baseline to ctDNA-negative following neoadjuvant paclitaxel, trastuzumab, and pertuzumab, consistent with the favorable long-term clinical outcomes.
- Clinical Relevance: These findings provide long-term support for chemotherapy de-escalation in selected patients with HER2-positive early breast cancer and suggest that biomarkers such as ctDNA may further refine individualized treatment strategies.
Paolo Tarantino, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses 5 year follow-up results from the phase 2 DAPHNe trial evaluating chemotherapy de-escalation with neoadjuvant paclitaxel, trastuzumab, and pertuzumab in patients with stage II and III HER2-positive breast cancer.
Results demonstrated excellent outcomes following omission of additional adjuvant chemotherapy in patients who achieved a pathologic complete response, with a 98% 5-year recurrence-free interval, only 1 local recurrence, and no distant recurrences. Dr Tarantino also reviews ultra-sensitive ctDNA findings, which showed clearance of detectable ctDNA in nearly all patients after neoadjuvant paclitaxel, trastuzumab, and pertuzumab, and discusses how ongoing studies may further establish chemotherapy de-escalation and biomarker-guided treatment selection in HER2-positive breast cancer.
Transcript:
Hi everyone, this is Paolo Tarantino from the Dana-Farber Cancer Institute. Glad to have an opportunity to highlight a recent publication of DAPHNe.
This was a phase 2 trial that looked at patients with stage II and III HER2-positive breast cancer treated with neoadjuvant paclitaxel, trastuzumab, pertuzumab (THP) for 12 weeks, and if they achieved pathologic complete response (pCR) no further chemotherapy in the adjuvant setting. The primary end point of the trial was published a few years ago, but now we published 5 year outcomes from the trial and also ultra-sensitive ctDNA analysis.
The trial overall enrolled 98 patients, mostly with stage II breast cancer. In this population, about half achieved pCR, but at 5 years what we saw is that outcomes were outstanding. The 5-year recurrence-free interval was 98%. There was only 1 recurrence, and it was a local recurrence, which was resected. There were no distant recurrences at 5 years with THP.
Despite pCR being a validated prognostic index, we know that beyond that we can look at additional measures of the biology of these tumors, which is why we looked at ctDNA here with an ultra-sensitive assay, NeXT personal Dx. What we found is that the totality of patients had positive ctDNA at baseline, before THP, but after neoadjuvant THP for 12 weeks almost all patients achieved conversion to negative ctDNA, which tracks very nicely with the outcomes we saw in terms of survival.
This was a small pilot cohort, not practice changing, but I do think it supports the results from also the largest CompassHER2 pCR trial. Over 2,000 patients treated with this exact regimen, 12 weeks of THP, showing also that about half of patients achieve pCR, and we still don't have long-term outcomes. But if CompassHER2 pCR confirms what we found in DAPHNe, and published in JAMA Oncology, that there are very few recurrences, in our case, no distant recurrences, that may become a standard of care for patients with low risk stage II HER2 positive breast cancer.
For patients with stage III or high risk stage II, adding 4 cycles of THP, as done in the DESTINY-Breast11 trial, may also be a way forward. And truthfully, I think not only anatomy but also biology will help us understand what treatment to give to each patient: ctDNA may help, HER2DX may help, tumor infiltrating lymphocytes may help.
I think we are reaching an era of tailored treatment for HER2-positive breast cancer, where we not only care about preventing recurrences but also optimizing the intensity of treatment, preventing unnecessary toxicities. All of this is ongoing, but I'm very glad to have the opportunity to mention DAPHNe, because I do think it's one of the steps that hopefully are going to take us there, where we really optimize treatments.
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
