Markers to Evaluate the Efficacy of PH-based Regimen as a Neoadjuvant Therapy for Operable HER2 Positive Breast Cancer

Official title

Gene Expression Assays and 68 Ga-Affibody HER-2 Imaging PET in Predicting Response to Treatment With Trastuzumab and Pertuzumab Before Surgery in Chinese Patients With HER2 Positive Breast Cancer

Overview

This study is to explore the markers in early prediction of the efficacy of pre-operative pertuzumab plus trastuzumab (PH) combined with chemotherapy for early stage or locally advanced human epidermal growth factor receptor-2 (HER-2) positive primary breast cancer.

Detailed description

This study is to evaluate the correlation between early changes in multiple markers and pathological complete response in breast and lyphm nodes (tpCR) in patients with HER2-positive breast cancer receiving carboplatin, docetaxel and trastuzumab plus pertuzumab (TCHP) pre-operatively. The markers would be examined by gene expression assays, fluorodeoxyglucose positron emission tomography (18F-FDG-PET), 68 Ga-Affibody HER-2 Imaging PET, and organoid drug sensitivity test. Approximately 94 patients were treated with PH-based neoadjuvant therapy followed by surgery, and would complete 1 year of PH-based regimen in the adjuvant setting. The primary endpoint is the percent change of SUVmax from baseline to Day 15 (after the first cycle of anti HER-2 targeting drug treatment) on FDG PET and HER-2 imagining PET in correlation with pathological complete response (pCR) in patients treated with preoperative pertuzumab and trastuzumab. pCR was defined as no viable invasive cancer in breast and axilla by local pathology review.

Interventions

• Diagnostic test TCHP
  Drug: Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV Other Name: Herceptin Drug: Pertuzumab 840 mg as a loading dose, then 420 mg every 3 weeks, IV Other Name: Perjeta Drug: carboplatin at target area under the plasma concentration-time curve (AUC) 6 Drug: docetaxel at a starting dose of 75 mg/m2 then to 60mg/m2 (q3w). All study drugs were administered intravenously. Procedure: 18-FDG-PET and 68 Ga-Affibody HER-2 Imaging PET will be performed at baseline, on day 15 and bef

Primary outcome measures

• Percent Change in Standardized Uptake Value (SUV) on Positron Emission Tomography and Change in Gene Expression With Response [Time frame: From baseline to day 15]

Secondary outcome measures (4)

• Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0) [Time frame: Immediately after the surgery]
• Invasive disease-free survival (iDFS) (excluding Second Primary Non-Breast Cancer [SPNBC]) [Time frame: Following surgery until Year 5]
• iDFS (including SPNBC) [Time frame: Following surgery until Year 5]
• Overall survival (OS) [Time frame: Following surgery until Year 5]

Eligibility criteria

Inclusion criteria

• Female or male, presenting for the first time with operable breast cancer, who had not received any previous treatment for an invasive malignancy.
• Primary tumor greater than (>) 2 cm in diameter.
• Age ≥ 18 years and < 70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1.
• Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55%
• Availability of tumor tissue specimen after surgery.
• Participants agree to undergo a core needle biopsy for genomic testing and organoid drug sensitivity assay.
• Histologically proven diagnosis of breast cancer.
• Patients have HER2-positive disease. HER2-positive disease was defined as follows: disease which overexpresses HER-2 by immunohistochemistry (IHC) 3+ and/or has HER2 amplification according to fluorescence in situ hybridization (FISH).
• Had hormonal receptors (ER and PgR) assessed.
• Signed informed consent.
• Able to comply with the protocol.

Exclusion criteria

• Metastatic disease (Stage IV) or bilateral breast cancer.
• Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer.
• Prior breast or non-breast malignancy within 5 years prior to study entry.
• Inadequate bone marrow, renal, or liver function
• History or evidence of cardiovascular condition
• Severe, uncontrolled systemic disease
• Participants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications.
• Pregnancy or breast-feeding women.
• Participants who received any investigational treatment within 4 weeks of study start.
• Participants with known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
• Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone or equivalent \[excluding inhaled steroids\]).
• Known hypersensitivity to any of the study drugs or excipients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

China · 1 center

• Shanghai Cancer Center, Fudan University — Shanghai

Publications

• Yang B, Chen M, Li P, Xiao X, Xiu B, Bai J, Sun Y, Xu X, Zhang J, Qiao Y, Xue J, Shao Z, Song S, Wu J. A prospective single-center cohort study: integrating PET imaging and genomics to identify early biomarkers of response to dual-targeted PH neoadjuvant therapy in breast cancer. Int J Surg. 2026 Feb 1;112(2):3312-3324. doi: 10.1097/JS9.0000000000003931. Epub 2025 Nov 11. PMID 41231642

Identifiers

NCT: NCT04281641 · SCHBCC-NO28

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗