neratinib dose escalation regimen for her2 positive early breast cancer

Conditions: HER2-positive Breast Cancer

Summary: this is a prospective study on the prevention of neratinib-related diarrhea in a chinese population, exploring the best options for reducing the incidence of neratinib-related diarrhea through either pharmacologic intervention (prophylactic antidiarrheal therapy) or non-pharmacologic intervention (dose escalation program).

this is a prospective, randomized, single-center clinical trial, divided into 3 groups (experimental group: group a and group b, control group: group c), planned sixty patients were enrolled, with 20 patients in each group. experimental group: group a (n=20) and group b (n=20) were given neratinib dose escalation regimen foranti-her2 adjuvant therapy.in group a, the dose of neratinib climbed up to 240mg within 2 weeks, and in group b, the dose climbed up to 240mg within 4 weeks. control group: group c (n=20) was given 240mg neratinib initially, but prophylactic loperamide antidiarrhea treatment was given at the same time within 2 months. diarrhea caused by neratinib often occurred within 1-2 months of initial treatment, so small dose of neratinib was used in both group a and group b at the time of initial treatment. the incidence and severity of neratinib-related diarrhea in the three groups were observed, and dfs and other neratinib-related adverse events were followed up for a long time. the study is to evaluate the safety and efficacy of neratinib dose escalation regimen and conventional dose combined with loperamide regimen in enhanced anti-her2 adjuvant therapy for early her2-positive breast cancer.

Eligibility criteria:
inclusion criteria: * age between 18 and 75 year-old women； * ecog score: 0-1； * her2 positive breast cancer diagnosed histologically is defined as her2 (3+) by immunohistochemistry or her2 (2+) with positive fish test； * postoperative pathological stage ⅱ → ⅲ, or initial stage (before neoadjuvant therapy) ⅱ → ⅲ, radiographic assessment showed no metastasis; * complete 1 year of anti-her2 therapy with trastuzumab, prior use of pertuzumab neoadjuvant + adjuvant therapy or t-dm1 adjuvant therapy is permitted; * no major organ dysfunction, contraception; * the patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the informed consent form. exclusion criteria: * patients who are allergic to the study drug, cannot take the drug orally, or refuse the medication regimen; * prior treatment with tki anti-her-2 drugs (e.g. lapatinib, pyrotinib, etc.); * patients were enrolled in other studies or stopped taking other drugs within 4 weeks; * patients with serious dysfunction of important organs (heart, liver and kidney); * patients with other malignancies, other than cured non-melanoma skin cancer, carcinoma in situ of the cervix and other tumors that have been cured for at least 5 years; * in pregnancy, lactation patients; * in the active stage of other acute or chronic infectious diseases; * the patients have uncontrollable mental illness; * there is a known history of human immunodeficiency virus; * there are other circumstances in which the investigator suggested that the patient should not participate in the study.