Treatment for hormone receptor positive HER2 positive breast cancer after neoadjuvant therapy

A Randomized, Open-Label, Phase III Trial Comparing Adjuvant Trastuzumab Plus Neratinib Versus Trastuzumab Plus Pertuzumab in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer With Residual Cancer Burden 0/I After Neoadjuvant Trastuzumab Plus Pertuzumab

This study is testing if combining two drugs, trastuzumab and nelatinib, can help people with hormone receptor positive HER2 positive breast cancer who still have cancer after initial treatment feel better compared to the usual combination of trastuzumab and pertuzumab.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: trastuzumab, pertuzumab, pyrotinib, lapatinib, neratinib, chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou)
• Trial ID: NCT05760612 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the efficacy and safety of combining trastuzumab with nelatinib in patients with hormone receptor positive HER2 positive breast cancer who have residual disease after neoadjuvant treatment. The study focuses on patients classified with RCB1-2, aiming to determine if this combination therapy is more effective than trastuzumab combined with parstuzumab. The approach is novel as it explores the use of a targeted therapy alongside a tyrosine kinase inhibitor in a specific patient population. The study is designed as a Phase 3 interventional trial to provide robust data on treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 18 to 70 with hormone receptor positive HER2 positive breast cancer and RCB classification 1-2 after neoadjuvant treatment.

Not a fit: Patients with early-stage breast cancer who do not meet the RCB classification criteria or have no residual disease after neoadjuvant treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with residual HER2 positive breast cancer after initial therapy.

How similar studies have performed: While there is limited data on this specific combination, similar studies exploring targeted therapies in HER2 positive breast cancer have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Female patients aged 18-70 years;
2. Eastern Cooperative Oncology Group performance status of 0 or 1;
3. Clinical stage at initial diagnosis (per the 8th edition of the American Joint Committee on Cancer Staging Manual): cT1-4/N1-3/M0 (cT1mi/N0 or cT1a-b/N0 are eligible), meeting the criteria for neoadjuvant therapy as per NCCN 2022 guidelines;
4. Histologically confirmed hormone receptor-positive (estrogen receptor ≥1% and/or progesterone receptor ≥1%) and HER2-positive (immunohistochemistry 3+ or fluorescence in situ hybridization-positive) invasive breast cancer;
5. Completion of ≥4 cycles of neoadjuvant therapy with trastuzumab and pertuzumab, without recurrence or metastatic disease prior to adjuvant treatment; residual cancer burden class 0 or I after neoadjuvant therapy; time from initial surgery to randomization ≤12 weeks;
6. Adequate organ function within 2 weeks prior to screening (without transfusion or use of growth factors):

   * Absolute neutrophil count ≥1.5 × 10⁹/L;
   * Platelet count ≥90 × 10⁹/L;
   * Hemoglobin ≥90 g/L;
   * Total bilirubin ≤1.5 × upper limit of normal (ULN);
   * Alanine aminotransferase and aspartate aminotransferase ≤1.5 × ULN;
7. Post-neoadjuvant therapy echocardiography showing left ventricular ejection fraction (LVEF) ≥50% during screening, with an absolute decrease of ≤15% compared to pre-chemotherapy values; if no pre-chemotherapy LVEF assessment is available, LVEF must be ≥55% during screening;
8. Life expectancy ≥6 months;
9. For premenopausal or non-sterilized female patients: agreement to abstain from sexual activity or use effective non-hormonal contraception during study treatment and for 8 weeks after the last dose;
10. Willingness to participate voluntarily, provide signed informed consent, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. History of local or regional breast cancer recurrence;
2. Clinical stage IV (metastatic) breast cancer;
3. Bilateral breast cancer;
4. History of other malignant tumors within the past 5 years, except for curatively treated cervical carcinoma in situ, basal cell carcinoma, or cutaneous squamous cell carcinoma;
5. Prior treatment with pyrotinib, lapatinib, neratinib, or other tyrosine kinase inhibitors; trastuzumab emtansine; or any antitumor biological or immunotherapy;
6. Concurrent participation in another clinical trial involving antitumor therapy, including endocrine therapy, bisphosphonate therapy, or immunotherapy;
7. Significant cardiac disease, including:

   * Heart failure or systolic dysfunction (LVEF \< 50%);
   * Poorly controlled arrhythmias (e.g., atrial tachycardia, significant ventricular arrhythmia, or high-grade atrioventricular block);
   * Angina requiring antianginal medication;
   * Clinically significant valvular heart disease;
   * Electrocardiographic evidence of transmural myocardial infarction;
   * Poorly controlled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 100 mmHg) despite medication;
8. Impaired drug absorption due to dysphagia, intestinal obstruction, or other gastrointestinal disorders;
9. History of neurological or psychiatric conditions that may compromise compliance or informed consent;
10. Chronic gastrointestinal disorders with predominant diarrhea;
11. Known hypersensitivity to any study drug components; history of immunodeficiency (e.g., HIV positivity, congenital or acquired immunodeficiency disorder), or prior organ transplantation;
12. Pregnancy, lactation, or positive pregnancy test at baseline in women of childbearing potential;
13. Severe comorbidities that may interfere with treatment, including active infections (e.g., hepatitis B, hepatitis C, tuberculosis, syphilis) or any other condition deemed by the investigator to render the patient unsuitable for trial participation.

Where this trial is running

Guangzhou

• Sun Yat-sen University Sun Yat-sen Memorial Hospital — Guangzhou, China (Recruiting)

Study contacts

• Study coordinator: Chang Gong

Conditions Early-stage Breast Cancer; HER2-positive Breast Cancer; Adjuvant Treatment After Trastuzumab; RCB Classification 1-2; Neratini; Hormone receptor positive HER2 positive breast cancer; targeted therapy; adjuvant therapy