Neoadjuvant Therapy for HER2-Positive Breast Cancer: THP Shows Promise, Offering Alternative to Carboplatin

A recent phase 3 clinical trial, neoCARHP, has demonstrated that a chemotherapy regimen of taxane, trastuzumab, and pertuzumab (THP) is non-inferior to the standard treatment of taxane, carboplatin, trastuzumab, and pertuzumab (TCbHP) for patients with stage II or III HER2-positive breast cancer. The findings, published in the Journal of Clinical Oncology, also suggest that THP offers a more tolerable treatment option with fewer side effects.

Understanding the neoCARHP Trial

The neoCARHP trial was a multicenter, open-label, randomized study conducted in China between April 2021 and August 2024. A total of 766 patients with previously untreated HER2-positive invasive breast cancer were enrolled and randomly assigned to receive either six 3-week cycles of THP (n=382) or TCbHP (n=384). Randomization was stratified by hormone receptor (HR) status and nodal status. 1

Treatment Regimens

• THP: Investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) combined with trastuzumab and pertuzumab, without carboplatin.
• TCbHP: Investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel) plus carboplatin, combined with trastuzumab and pertuzumab.

Key Findings: Non-Inferiority and Improved Tolerability

The primary endpoint of the trial was the pathologic complete response (pCR) rate – the absence of invasive cancer in the breast and axilla following neoadjuvant therapy. Results showed:

• THP Group: pCR was achieved in 64.1% of patients (95% Confidence Interval: 59.1%–69.0%).
• TCbHP Group: pCR was achieved in 65.9% of patients (95% Confidence Interval: 60.9%–70.6%).

The absolute difference in pCR rates between the two groups was -1.8% (95% CI: -8.5% to 5.0%), demonstrating non-inferiority of THP to TCbHP (P for noninferiority = .0089). 3

Importantly, patients receiving THP experienced fewer and less severe side effects. Grade 3 or 4 treatment-related adverse events occurred in 20.7% of the THP group compared to 34.6% of the TCbHP group. Common adverse events in the THP group included neutropenia, leukopenia, and diarrhea, all occurring at lower rates than in the TCbHP group. 1 No treatment-related deaths were reported in either arm.

Subgroup Analysis

Further analysis revealed that THP remained non-inferior across various subgroups, including age, T stage, and nodal status. In patients with hormone receptor-negative tumors, pCR rates were comparable between the THP and TCbHP arms (78.2% vs 77.8%). While pCR rates were slightly lower in the hormone receptor-positive subgroup with THP (55.8%) compared to TCbHP (58.8%), the difference was not statistically significant. 1

Implications for HER2-Positive Breast Cancer Treatment

The neoCARHP trial suggests that THP represents a viable alternative to TCbHP for patients with stage II or III HER2-positive breast cancer. By omitting carboplatin, THP offers the potential for reduced toxicity and improved quality of life without compromising treatment efficacy. Ongoing trials are further investigating the possibility of de-escalating treatment cycles in HER2-positive breast cancer. 2

This research was also presented at ASCO 2025, highlighting the significance of these findings for the breast cancer community. 4