THP Yields Noninferior pCR vs TCbHP in HER2-Positive Early Breast Cancer

The phase 3 neoCARHP trial (NCT04858529) found that investigator-selected taxane plus trastuzumab (Herceptin) and pertuzumab (Perjeta; THP) provided noninferior pathological complete response (pCR) rates and improved tolerability compared with taxane, carboplatin, trastuzumab, and pertuzumab (TCbHP) for patients with HER2-positive breast cancer.

neoCARHP Trial Results

In the modified intention-to-treat (mITT) population, 64.1% of patients (95% CI, 59.1%-69.0%) in the THP group achieved a pCR. This was compared with 65.9% of patients (95% CI, 60.9%-70.6%) in the TCbHP group. The absolute difference between the groups was –1.8% (95% CI, –8.5 to 5.0; P_{noninferiority} = .0089). Because the lower bound of the 95% CI (–8.5%) was within the prespecified noninferiority margin of –10%, the study met its primary objective.

Secondary analyses of the per-protocol set further reinforced these results, showing identical pCR rates of 68.5% in both the THP and TCbHP groups (absolute difference, 0.0%; 95% CI, –6.8% to 6.8%; P_{noninferiority} = .002). Subgroup analyses indicated that THP remained noninferior across most clinically relevant categories, including age, T stage, and nodal status. Among patients with hormone receptor (HR)–negative tumors, pCR was achieved by 78.2% in the THP arm vs 77.8% in the TCbHP arm (absolute difference 0.4%; 95% CI, –9.2% to 10.0%). In the HR-positive subgroup, pCR rates were 55.8% and 58.8%, respectively (absolute difference –3.0%; 95% CI, –11.7% to 5.9%).

neoCARHP Design and Details

The neoCARHP trial was an open-label, randomized, phase 3 noninferiority study. Patients were randomly assigned in a 1:1 ratio to receive six 3-week cycles of either TCbHP or THP. Randomization was stratified by HR status and nodal status.

In the TCbHP arm, patients received an investigator-selected taxane—docetaxel (75 mg/m²), paclitaxel (175 mg/m²), or nab-paclitaxel (Abraxane; 260 mg/m²)—plus carboplatin (AUC 6) every 3 weeks. In the THP arm, patients received the same investigator-selected taxane—docetaxel (100 mg/m²), paclitaxel (175 mg/m²), or nab-paclitaxel (260 mg/m²)—without carboplatin. Both groups received concurrent intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. Definitive surgery was scheduled within 6 weeks of completing neoadjuvant therapy.

Patient Population

The trial enrolled women aged 18 years or older with previously untreated, stage II or III HER2-positive invasive breast cancer. Patients with stage IV disease, inflammatory breast cancer, or bilateral breast cancer were excluded.

The mITT population included 766 patients (382 in the THP group and 384 in the TCbHP group). The median age was 52 years in the THP group and 51 years in the TCbHP group. Most patients had stage II disease (77.0% vs 71.6%) and T1-2 tumors (81.4% vs 78.6%). Nodal status was positive in 64.1% of patients in both arms. Regarding HR status, 62.8% of the THP group and 62.5% of the TCbHP group had estrogen receptor–positive and/or progesterone receptor–positive disease.

End Points

The primary end point was locally determined pCR, defined as the absence of invasive cancer in the breast and axilla (ypT0/is ypN0). Secondary end points included clinical response rate per RECIST v1.1 criteria, the rate of breast-conserving surgery, event-free survival, invasive disease-free survival, overall survival, and safety.

Safety

The THP regimen demonstrated a more favorable safety profile than TCbHP. Grade 3 or higher adverse events (AEs) occurred in 20.7% of the THP group compared with 34.6% of the TCbHP group. Serious AEs (SAEs) were reported in 1.3% of patients receiving THP vs 4.7% of those receiving TCbHP.

The most frequent grade 3 or 4 AEs in the THP and TCbHP groups, respectively, included:

• Neutropenia: 6.9% vs 16.4%
• Leukopenia: 5.5% vs 14.8%
• Diarrhea: 2.6% vs 4.2%

Dose reductions for the taxane were required for 8.1% of patients in the THP group. In the TCbHP group, 25.3% of patients required dose reductions, primarily due to carboplatin (15.1% for carboplatin alone; 9.1% for both agents). There were no treatment-associated deaths reported in either group.

Reference

Gao HF, Ye GL, Lin Y, et al. Neoadjuvant taxane plus trastuzumab and pertuzumab with or without carboplatin in human epidermal growth factor receptor 2-positive breast cancer: the randomized noninferiority phase III neoCARHP Trial. J Clin Oncol. Published online January 23, 2026. doi:10.1200/JCO-25-02176