# Translational and real-world evidence of trastuzumab biosimilar CT-P6 plus pertuzumab in neoadjuvant HER2-positive early breast cancer

## TL;DR

This study shows that CT-P6 biosimilar with pertuzumab is effective and safe for early HER2-positive breast cancer treatment, achieving high pathologic complete response rates.

## Contribution

The study provides real-world evidence of CT-P6 biosimilar efficacy and safety in neoadjuvant HER2-positive breast cancer treatment.

## Key findings

- 57.43% of patients achieved pathologic complete response (pCR) with CT-P6 plus pertuzumab and chemotherapy.
- No significant differences in pCR were found between anthracycline-based and non-anthracycline-based regimens.
- Treatment was well-tolerated with minimal Grade 3–4 adverse events and no immunogenicity or cardiotoxicity observed.

## Abstract

Data on neoadjuvant treatment with trastuzumab biosimilars, particularly CT-P6, in combination with pertuzumab, are limited. This study evaluates the efficacy, tolerability, and immunogenicity of CT-P6 plus pertuzumab and chemotherapy, in routine clinical practice for HER2-positive early breast cancer, including translational biomarker analyses related to pathologic complete response (pCR).

Prospective, multicenter, observational study in 102 patients with HER2-positive early breast cancer. Patients received hospital-preferred neoadjuvant regimens protocols, with (scheme 1 and 3) or without anthracyclines (scheme 2). The primary endpoint was pCR, defined as the absence of invasive tumor in both the breast and axillary lymph nodes (ypT0/ypTis and ypN0). Translational endpoints included soluble HER2, anti-trastuzumab CT-P6 antibodies, and exploratory response-related modeling approaches supported by machine learning techniques.

Among patients who underwent surgery, pCR (ypT0/ypTis and ypN0) was achieved in 57.43% of cases, with no significant differences between anthracycline-based and non-anthracycline-based regimens. Soluble HER2 and anti-trastuzumab CT-P6 antibodies were not significantly associated with pCR. Treatment was well-tolerated; the most relevant Grade 3–4 treatment-related adverse events were diarrhea (2.25%) and asthenia (0.50%). No immunogenicity or clinically relevant cardiotoxicity was observed.

Trastuzumab CT-P6 combined with pertuzumab and chemotherapy can be used in neoadjuvant treatment for HER2-positive early breast cancer, showing pCR rates comparable to the reference trastuzumab and without evidence of immunogenicity. Exploratory analyses of soluble HER2 and anti-trastuzumab CT-P6 antibodies did not demonstrate a significant association with pCR, although this possibility cannot be excluded. Their assessment contributes to the translational understanding of biosimilar integration into curative regimens.

The study has been registered in Clinicaltrials.gov (https://clinicaltrials.gov/study/NCT06907082).

The online version contains supplementary material available at 10.1007/s10549-026-07895-8.