Auricular Point Stimulation Plus Dexamethasone Versus Standard Antiemetic Regimen for Nausea and Vomiting Caused by Trastuzumab Deruxtecan

Trastuzumab deruxtecan is an important therapeutic agent in the palliative treatment of advanced breast cancer. It is used as first-line therapy for HER2-positive advanced breast cancer in patients who have previously received anti-HER2 treatment, as well as second-line or later therapy for advanced or recurrent breast cancer. Additionally, it is the first targeted therapy approved in China for HER2-low advanced breast cancer. While it improves patient survival rates, it is also associated with certain gastrointestinal adverse reactions, with treatment-related nausea and vomiting being particularly common, occurring in nearly 80% of cases. The majority of these symptoms occur on the day of administration and within the following four days. This regimen is currently classified as a high-emetogenic-risk treatment in clinical guidelines. The recommended prophylactic antiemetic strategy typically involves a quadruple regimen combining corticosteroids (e.g., dexamethasone), 5-HT3 receptor antagonists (e.g., ondansetron, palonosetron), NK1 receptor antagonists (e.g., fosaprepitant, aprepitant), and the antipsychotic drug olanzapine. However, in clinical practice, many patients experience drug-related gastrointestinal adverse reactions such as anorexia, bloating, constipation, and diarrhea due to the use of high-intensity antiemetic therapy. Studies have shown that the incidence of constipation in chemotherapy patients treated with palonosetron nearly doubles. The aggressive use of antiemetics severely impacts patients' gastrointestinal function, quality of life, and even their treatment adherence. Therefore, how to effectively prevent trastuzumab deruxtecan-induced nausea and vomiting while minimizing the side effects of antiemetic therapy itself has become a practical issue that healthcare professionals urgently need to address. Auricular point pressotherapy is a traditional Chinese medicine (TCM) external therapy. It involves accurately pasting Vaccaria seeds on corresponding auricular points with adhesive tapes and stimulating the points through moderate pressing to regulate physical functions and treat diseases. According to TCM theory, the ear is closely connected to the internal organs and meridians of the human body, and all twelve meridians are directly or indirectly linked to the ear. Auricular point pressotherapy can unblock meridians and balance yin and yang by stimulating corresponding auricular points, thereby alleviating anti-cancer therapy-related nausea and vomiting and other adverse reactions. It is an economical, non-invasive, and low-side-effect natural therapy. Meanwhile, auricular point pressotherapy can effectively improve gastrointestinal function, thus significantly reducing gastrointestinal dysfunction caused by chemotherapy and antiemetic drugs, such as anorexia, abdominal distension, constipation, and diarrhea. Our team summarized the relevant data of patients who voluntarily received auricular point pressotherapy for antiemesis previously. The results showed that among breast cancer patients who received trastuzumab deruxtecan. 100% of those treated with auricular point pressotherapy plus dexamethasone did not experience grade 2 or above (including grade 2) nausea and had no vomiting on the day of medication and within 3 days thereafter.

Based on the above theoretical and practical basis, this study intends to evaluate whether the preventive and suppressive effects of auricular point stimulation combined with dexamethasone on the CINV induced by trastuzumab deruxtecan are non-inferior to the standard antiemetic regimen in the palliative treatment of breast cancer. Additionally, it will assess patients' appetite, gastrointestinal function, and other related indicators, and explore the significant role of integrated traditional Chinese medicine and Western medicine interventions in improving patients' quality of life during anti-cancer treatment, thereby providing a clinical reference for optimizing the management of adverse reactions of trastuzumab deruxtecan treatment.

Inclusion criteria

• Patients must meet the following inclusion criteria for the study: * Age ≥ 18 years and ≤ 85 years; * Breast cancer patients scheduled to undergo palliative treatment with trastuzumab deruxtecan; * ECOG performance status score of 0-2; * Normal hematological function (platelet count > 80×10⁹/L; white blood cell count > 3×10⁹/L; neutrophil count > 1.5×10⁹/L); * Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), and transaminase ≤ 5 times the ULN; * No ascites, no gastrointestinal obstruction, normal coagulation function, and serum albumin ≥ 30g/L; * Child-Pugh classification of liver function is Grade A; * Serum creatinine < ULN, or calculated creatinine clearance rate > 50ml/min.

Exclusion criteria

• Patients who meet any of the following criteria will be excluded from the study: * Local inflammation or infection of the auricle; * Bleeding tendency or coagulation disorders; * Severe ascites; * Gastrointestinal obstruction; * Hypertensive crisis or hypertensive encephalopathy; * Severe uncontrolled systemic complications such as infection or diabetes mellitus; * Clinically severe cardiovascular diseases, including cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), hypertension that is not well-controlled despite appropriate medication, unstable angina pectoris, congestive heart failure (NYHA Class 2-4), and cardiac arrhythmias requiring drug treatment; * A history of or physical examination findings indicating central nervous system diseases (e.g., primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastasis or stroke); * Hypersensitivity to any drugs used in the study; * Pregnant or lactating women; * Presence of any other diseases, functional impairment caused by metastatic lesions, or suspicious disorders identified during physical examination, which suggest contraindications to the study drugs or place the patient at high risk of treatment-related complications; * Inability or unwillingness to comply with the study protocol.