Pertuzumab numerically improved IDFS in all subgroups, greatest in HER2 FISH-low/ER-positive tumors. These exploratory findings are hypothesis-generating and support prospective validation of biomarker-guided strategies.

P2, N=393, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2026 --> Mar 2026

Among targeted therapy regimens, patients in the HER2 3+ group receiving dual-target therapy with trastuzumab plus pertuzumab had a higher pCR rate compared to trastuzumab monotherapy (63.0% vs. 46.2%, P = 0.008), while patients in the HER2 2+/FISH+ group did not show significant benefit from dual-target therapy (31.8% vs. 26.5%, P = 0.774). These findings suggest limitations in current anti-HER2 therapy based on the existing HER2 classification. Future strategies should incorporate HER2 expression level and HR status to develop more precise individualized treatment plans.

P3, N=230, Recruiting, Hoffmann-La Roche | Trial primary completion date: Sep 2026 --> Dec 2026

Metastasis-directed local therapy and treatment regimen (trastuzumab vs. trastuzumab + pertuzumab) were not independently associated with NED attainment or PFS...Radiologic NED was independently associated with prolonged PFS within this enriched population. Factors associated with NED attainment included favorable ECOG performance status, HER2 IHC 3+ expression, and high tumor grade; given the wide confidence intervals, these estimates should be interpreted cautiously as exploratory and hypothesis-generating.

This multicenter retrospective study included 290 female patients diagnosed with HER2-positive early or locally advanced breast cancer treated with neoadjuvant trastuzumab and pertuzumab-based regimens (anthracycline-based [AC-THP] or non-anthracycline [TCHP]) across six centers. pCR remains the strongest surrogate for survival, neutralizing initial risk factors. These findings support using quantitative biomarker thresholds for personalization and reinforce the efficacy of non-anthracycline regimens.

Anthracycline-free THP is a highly active, well-tolerated neoadjuvant option for HER2-positive EBC, with particularly high pCR rates in HR-negative disease. HR status emerged as a key determinant of pCR, whereas the role of PIK3CA mutations remains inconclusive and requires confirmation in larger prospective studies.

P1, N=24, Not yet recruiting, Shanghai Henlius Biotech

Neoadjuvant therapy with dual human epidermal growth factor receptor 2 (HER2) blockade using trastuzumab and pertuzumab combined with chemotherapy is the standard of care for patients with locally advanced HER2-positive breast cancer...HR status is a strong and independent predictor of pCR in HER2-positive breast cancer patients receiving neoadjuvant dual blockade. Patients with HR- disease derive the most benefit from this regimen, highlighting the need for tailored therapeutic strategies to improve outcomes for the HR+ subgroup.

P3, N=55, Terminated, Biocon Biologics UK Ltd | N=382 --> 55 | Trial completion date: Nov 2026 --> Dec 2025 | Recruiting --> Terminated; US FDA is streamlining the Biosimilar development. Thus, Biocon decided to terminate the study.

P=N/A, N=42, Not yet recruiting, Peking University Cancer Hospital & Institute