Neoadjuvant THP Is Noninferior to Standard TCbHP in HER2+ Breast Cancer

The neoadjuvant combination of a taxane plus trastuzumab (Herceptin) and pertuzumab (Perjeta; THP) demonstrated noninferior pathologic complete response (pCR) rates compared with the standard 4-drug regimen of a taxane, carboplatin, trastuzumab, and pertuzumab (TCbHP) for patients with stage II or III HER2-positive breast cancer, according to findings from the phase 3 neoCARHP trial (NCT04858529) published in the Journal of Clinical Oncology.¹

The primary end point of pCR in the breast and axilla was achieved by 64.1% (95% CI, 59.1-69.0) of patients in the THP arm (n = 382) and 65.9% (95% CI, 60.9-70.6) of those in the TCbHP arm (n = 384; absolute difference, –1.8%; 95% CI, –8.5 to 5.0; P for noninferiority = 0.0089). Notably, the THP regimen was associated with significantly improved tolerability, with lower rates of grade 3 and 4 adverse effects (AEs; THP arm, 20.7% vs TCbHP arm, 34.6%) and serious AEs (1.3% vs 4.7%).

“The every-3-week THP achieved pCR rates comparable with those of the TCbHP regimen, [and simultaneously demonstrated] fewer grade 3 to 4 and serious AEs and [preserved] a convenient dosing schedule,” lead study author Hong-Fei Gao, MD, of the Department of Breast Cancer and the Cancer Center at Guangdong Provincial People's Hospital, and the Guangdong Academy of Medical Sciences Southern Medical University in Guangzhou, China, and coauthors wrote in the paper. “These findings support omitting carboplatin as a rational alternative strategy combined with dual HER2 blockade for HER2-positive early breast cancer.”

What was the rationale for investigating the omission of carboplatin in HER2-positive breast cancer?

Although TCbHP is a preferred neoadjuvant treatment option according to clinical guidelines, the therapeutic contribution of carboplatin has remained undetermined for many patients. Platinum agents are associated with higher incidences of grade 3 and 4 hematologic toxicities and gastrointestinal AEs, which frequently lead to treatment delays, dose reductions, or treatment discontinuation. The neoCARHP investigators hypothesized that dual HER2 blockade with trastuzumab and pertuzumab might be effective enough when paired with a single taxane to allow for the de-escalation of chemotherapy by removing carboplatin.

What was the design of the neoCARHP trial?

This multicenter, open-label, randomized trial enrolled women at least 18 years of age 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 either:

• TCbHP arm: investigator-selected taxane (docetaxel, paclitaxel, or nab-paclitaxel [Abraxane]) plus carboplatin, trastuzumab, and pertuzumab
• THP arm: investigator-selected taxane without carboplatin, plus trastuzumab and pertuzumab

The primary end point of pCR was assessed using the modified intent-to-treat population, consisting of all randomly assigned patients who received at least 1 dose of treatment. Secondary end points included clinical response rate, breast-conserving surgery rate, event-free survival, invasive disease–free survival, and safety.

What were the baseline characteristics of the neoCARHP trial population?

Between April 2021 and August 2024, 774 patients were enrolled across 15 hospitals in China. The median age was 52 years (IQR, 45-58) in the THP group and 51 years (IQR, 44-56) in the TCbHP group. Most patients in these respective arms had stage II disease (77.0% and 71.6%) and were node-positive (64.1% in both arms). Regarding hormone receptor (HR) status, 62.8% of patients in the THP arm and 62.5% of those in the TCbHP arm had HR-positive disease.

How did the neoCARHP efficacy findings compare across subgroups of patients with HER2-positive breast cancer?

The efficacy of the carboplatin-free regimen remained consistent across most clinically relevant patient subgroups. In patients with HR-negative tumors, the pCR rate was 78.2% with THP and 77.8% with TCbHP (absolute difference, 0.4%; 95% CI, –9.2 to 10.0). For those with HR-positive disease, pCR was achieved in 55.8% and 58.8%, respectively (absolute difference –3.0%; 95% CI, –11.7 to 5.9). Analysis of the per-protocol set further supported these findings, yielding identical pCR rates of 68.5% for both groups.

What was the safety profile of THP compared with TCbHP in the neoCARHP trial?

Dose reductions were required for only 8.1% of patients in the THP arm compared with 25.3% of those in the TCbHP arm.

Common grade 3 and 4 AEs reported in the THP and TCbHP arms, respectively, included:

• Neutropenia (6.9% vs 16.4%)
• Leukopenia (5.5% vs 14.8%)
• Thrombocytopenia (0.3% vs 4.2%)
• Anemia (2.1% vs 6.5%)
• Diarrhea (2.6% vs 4.2%)

Other any-grade nonhematologic toxicities, such as alopecia (72.5% vs 71.6%), neuropathy (43.7% vs 49.0%), and fatigue (41.9% vs 44.3%), occurred at comparable frequencies between the 2 groups. No treatment-related deaths occurred in either arm.

Further viewing: Following the initial presentation of the neoCARHP data at the 2025 ASCO Annual Meeting, OncLive® sat down with Paolo Tarantino, MD, PhD, a research fellow in the Department of Medicine at Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, to discuss the potential clinical implications of the data.²

“The major shift in clinical practice will be that many more patients will be considered for treatment with THP,” Tarantino said in the interview. “We are moving toward a paradigm where we start THP, after 4 cycles, we try to understand whether the tumor has completely disappeared. If it has not, we consider 2 more cycles of THP and then take [the patient] to surgery and see whether there is a pCR.”

References

1. 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
2. Tarantino P. Dr Tarantino on clinical implications of the neoCARHP trial in HER2+ breast cancer. OncLive.com. October 30, 2025. Accessed March 31, 2026. https://www.onclive.com/view/dr-tarantino-on-clinical-implications-of-the-neocarhp-trial-in-her2-breast-cancer