Event-free survival from the randomized phase 2 neoHIP trial evaluating neoadjuvant taxane, HER2-targeted therapy, +/- pembrolizumab in early-stage HER2-positive breast cancer.

623 Background: In early-stage HER2–positive breast cancer, achieving a pathological complete response (pCR) after neoadjuvant therapy is strongly associated with improved event-free survival (EFS); however, a substantial proportion patients (pts) fail to achieve pCR, requiring subsequent adjuvant systemic therapy and remaining at higher risk for recurrence. Pembrolizumab (pembro) is well-tolerated, invigorates anti-tumor immunity, and may enhance response of chemotherapy and/or anti-HER2. We previously reported the positive primary outcome of the randomized phase 2 neoHIP trial, showing an improvement in pCR with the addition of pembro to neoadjuvant paclitaxel, trastuzumab, and pertuzumab (4 cycles, THP–pembro, pCR: 67% v. THP: 48%, p=.026). With long-term follow-up now mature, we now report EFS outcomes. Methods: Pts aged ≥ 18 years with stage II–III HER2–positive breast cancer were randomized, stratified by hormone receptor status and nodal status, to receive neoadjuvant THP or THP–pembro. EFS was defined as the time from randomization to progression of disease precluding surgery, local or distant recurrence, or death from any cause. EFS was estimated using the Kaplan–Meier (KM) method and compared between arms using a two-sided stratified log-rank test. Data were analyzed with a cutoff date of January 23, 2026. Results: Among 116 pts (58 per arm) randomized to THP +/- pembro, median follow-up was 37 months (range, 33–43). The 36-month EFS rate was 95% (95% CI, 89–100) for THP and 100% (95% CI, 100–100) for THP-pembro, with a trend towards significance (p=.099). Three EFS events were observed, all occurring in the THP arm, with one death related to recurrence and n=2/3 events occurring in patients with non-pCR. Conclusions: THP + pembro was associated with 100% EFS after a median follow-up of 37 months, whereas recurrences were observed in the THP arm, consistent with historical EFS expectations for neoadjuvant chemotherapy + dual HER2-targeted therapy. Although not powered for EFS, these findings support definitive evaluation of THP +/- pembro in a phase III trial. Clinical trial information: NCT03747120 .