Efficacy and Safety of Probiotics Versus Standard Care in Preventing Diarrhea Induced by Neratinib in Breast Cancer Patients: A Prospective Randomized Controlled Clinical Trial
Design: This is a prospective, randomized controlled clinical trial. Participants will be randomly assigned to either a probiotics intervention group or a placebo-controlled group. Both groups will receive prophylactic loperamide according to the FDA-recommended dosing schedule for neratinib-associated diarrhea. Primary
Objective: To evaluate the efficacy of probiotics in reducing the incidence and severity of diarrhea in patients receiving Neratinib. Secondary
Objectives: This study will also investigate the effects of probiotics on gut microbiota composition and their potential impact on drug efficacy. Study Duration: Enrollment is planned from August 2025 to June 2027 at Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Both the intervention and control groups will receive treatment for a total of six weeks (two cycles of three weeks each). No post-treatment observation period is included. Eligibility Criteria: Participants must be diagnosed with HER2-positive breast cancer and scheduled to receive Neratinib. Exclusion criteria include patients with severe gastrointestinal disorders or recent probiotic consumption.
⁃ Participants must meet all of the following criteria:
• Female patients aged ≥18 years, diagnosed with HER2-positive breast cancer.
• Scheduled to receive Neratinib therapy (monotherapy or in combination), based on clinical guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, with an expected survival of at least 3 months.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• Resolution of any prior treatment-related toxicity to Grade ≤1 (per CTCAE v5.0), with AST and ALT ≤ 2.5 × the upper limit of normal (ULN), and total bilirubin ≤ 1.5 × ULN.
• Adequate bone marrow function, defined as:
• White blood cell count ≥ 3.0 × 10⁹/L Neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Hemoglobin ≥ 90 g/L Serum creatinine ≤ 1.5 × ULN
• No persistent gastrointestinal symptoms, such as hematochezia, chronic constipation, or abdominal pain.
• No evidence of structural gastrointestinal abnormalities confirmed by gastroscopy or other relevant examinations.