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

Clinical Snapshot

Key Findings

• P Value: P(noninferiority) = 0.0089

• Effect Size: Absolute difference -1.8% favouring TCbHP

• Primary Outcome: pCR rate: THP 64.1% (95% CI 59.1-69.0%) vs TCbHP 65.9% (95% CI 60.9-70.6%)

• Nnt Or Sensitivity: Non-inferiority margin met; OR 0.93 (95% CI 0.69-1.25)

• Confidence Interval: 95% CI: -8.5% to 5.0%

Clinical Application

High - all agents (trastuzumab, pertuzumab, taxanes) are PBS-subsidised and widely available in Australian cancer centres Aligns with current NCCN and ESMO guidelines. TGA-approved agents. May reduce chemotherapy-related hospitalisations and healthcare costs while maintaining efficacy Australian women with stage II-III HER2+ breast cancer suitable for neoadjuvant therapy

Abstract

PURPOSE: The neoCARHP aimed to investigate the efficacy and safety of investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus trastuzumab and pertuzumab, with carboplatin (TCbHP) or without carboplatin (THP), in stage II and III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: The neoCARHP was a multicenter, randomized, phase III, noninferiority study. Eligible patients were women age 18 years or older with previously untreated, stage II and III, HER2-positive invasive breast cancer. Patients were randomly assigned (1:1) to receive six 3-week cycles of TCbHP or THP. The primary end point was pathologic complete response (pCR) rate in the breast and axilla (ypT0/is ypN0) in the modified intention-to-treat (mITT) population (all randomly assigned patients receiving at least one dose of study treatment). Safety was evaluated in all patients who received any study treatment. RESULTS: Between April 30, 2021, and August 27, 2024, 774 patients were randomly assigned and 766 were included in the mITT population (382 in THP and 384 in TCbHP). pCR was achieved in 245 (64.1% [95% CI, 59.1 to 69.0]) patients in the THP group and 253 (65.9% [60.9-70.6]) in the TCbHP group (absolute difference, -1.8% [95% CI, -8.5 to 5.0]; odds ratio, 0.93 [95% CI, 0.69 to 1.25]; Pnoninferiority = .0089). The THP group had fewer grade 3 and 4 adverse events (20.7% v 34.6%) and serious adverse events (1.3% v 4.7%) than the TCbHP group. The most common grade 3 and 4 adverse events with THP were neutropenia (6.8% v 16.4% with TCbHP), leukopenia (5.5% v 14.8%), and diarrhea (2.6% v 4.2%). No treatment-associated deaths occurred. CONCLUSION: THP provided noninferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin may be applicable in HER2-positive breast cancer.

References

1. 1.Gao, H. F., Ye, G. L., Lin, Y., Huang, Q., Dong, J., Cao, Y., Zhao, Y. X., Chen, Q. J., Ma, S. H., Ouyang, J., Ye, J. H., Yang, H. W., Zhang, Y. Q., Zhang, Y. C., Zhang, G. L., Li, W., Zhang, Y., Wu, Z. Y., Lin, Y. Y., Zhu, T., Zhang, L. L., Yang, C. Q., Yang, M., Peng, H., Chen, B., Chen, Y. T., Ji, F., Cheng, M. Y., Li, J. Q., Jiang, Z., & Wang, K. (2026). 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. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-02176