Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer

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.