Clinical trial NCT05561686: Real-world Study of Pyrotinib in Neoadjuvant Therapy for HER2-positive Breast Cancer
Official title: Real-world Study of Pyrotinib in Neoadjuvant Therapy for HER2-positive Breast Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: HER2-positive Breast Cancer
Keywords: RWS
Pyrotinib
Neoadjuvant therapy
Lead sponsor: Hunan Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2022-09-30
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with HER2-positive breast cancer scheduled to receive pirotinib as neoadjuvant therapy

Brief summary: Pyrotinib is currently being investigated in both registration studies and investigator-initiated studies in the neoadjuvant and adjuvant setting for HER2-positive breast cancer, all of which are RCTs, but randomized clinical studies have selected specific populations in defined settings, which may differ from the actual clinical setting. Given the limited real-world data on pyrotinib, real-world studies focusing on neoadjuvant therapy have not been reported. At present, we hope to collect the data of neoadjuvant therapy for HER2-positive breast cancer patients who have been prescribed pyrotinib, and explore the efficacy and safety of pyrotinib-based neoadjuvant therapy for HER2-positive early or locally advanced breast cancer patients; exploratory analysis to explore the correlation between TMB levels and pCR rate of neoadjuvant therapy in HER2-positive breast cancer patients, and the effect of pyrotinib-based neoadjuvant therapy on intestinal flora.

Detailed description: Pyrotinib is a small molecule, irreversible, pan-ErbB receptor tyrosine kinase inhibitor that simultaneously acts on three targets, HER1, HER2, and HER4, and is stable, well tolerated, and easily penetrates the blood-brain barrier compared with macromolecular targeted drugs. In the phase II study of pyrotinib combined with capecitabine in HER2-positive breast cancer, the primary study endpoint ORR was 78.5%, and the investigator-assessed PFS reached 18.1 months with good safety; it was precisely by virtue of the phase II clinical study that the drug was preferentially approved by the State Drug Administration for marketing. During the four years of marketing, significant therapeutic effects have also been achieved in phase III clinical studies, such as the PHOEBE study and the PHENIX study; neoadjuvant treatment of patients with early and locally advanced HER2-positive breast cancer was approved for the PHEDRA study in 2022.

Pyrotinib is currently being investigated in both registration studies and investigator-initiated studies in the neoadjuvant and adjuvant setting for HER2-positive breast cancer, all of which are RCTs, but randomized clinical studies have selected specific populations in defined settings, which may differ from the actual clinical setting. Given the limited real-world data on pyrotinib, real-world studies focusing on neoadjuvant therapy have not been reported. At present, we hope to collect the data of neoadjuvant therapy for HER2-positive breast cancer patients who have been prescribed pyrotinib, and explore the efficacy and safety of pyrotinib-based neoadjuvant therapy for HER2-positive early or locally advanced breast cancer patients; exploratory analysis to explore the correlation between TMB levels and pCR rate of neoadjuvant therapy in HER2-positive breast cancer patients, and the effect of pyrotinib-based neoadjuvant therapy on intestinal flora.

Eligibility criteria: Inclusion Criteria:

1. age ≥ 18 years and ≤ 65 years
2. breast cancer meeting the following criteria: Histologically confirmed invasive breast cancer with a primary tumor \> 2 cm in diameter as determined by standard assessment at the site
3. HER2 expression positive breast cancer confirmed by pathological examination, defined as an immunohistochemical (IHC) score of 3 + in \> 10% of immunoreactive cells or HER2 gene amplification by in situ hybridization (ISH) results (HER2 gene signal to centromere 17 signal ratio ≥ 2.0 or HER2 gene copy number ≥ 6).
4. known hormone receptor status (ER and PgR);
5. The functional level of major organs must meet the following requirements (no blood transfusion within 2 weeks before screening, and no leukocyte-elevating or platelet-elevating drugs have been used):

1) Blood routine neutrophil (ANC) ≥ 1.5 × 10\^9/L; platelet count (PLT) ≥ 90 × 10\^9/L; hemoglobin (Hb) ≥ 90 g/L; 2) Blood biochemistry total bilirubin (TBIL) ≤ upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; 3) Echocardiography left ventricular ejection fraction (LVEF) ≥ 55%; 4) 12-lead electrocardiogram Fridericia-corrected QT interval (QTcF) \< 470 msec.

6. For female patients who are not postmenopausal or surgically sterile: agree to abstain from sexual activity or use an effective method of contraception during treatment and for at least 7 months after the last dose of study treatment.

7. Voluntarily join this study, sign the informed consent form, have good compliance and are willing to cooperate with the follow-up.

8. have received or plan to receive pyrotinib for neoadjuvant therapy 9. have a traceable medical history during treatment

Exclusion Criteria:

1. did not sign informed consent
2. stage IV (metastatic) breast cancer;
3. inflammatory breast cancer;
4. previous anti-tumor therapy or radiotherapy for any malignant tumor, excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma and other malignant tumors;
5. Major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures;
6. serious heart disease or discomfort, including but not limited to the following diseases:

   * Confirmed history of heart failure or systolic dysfunction (LVEF \< 50%);
   * High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate \> 100 bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher grade atrioventricular block (i.e. Mobitz II second-degree atrioventricular block or third-degree atrioventricular block);
   * Angina pectoris requiring antianginal medication; -- Clinically significant valvular heart disease;
   * ECG shows transmural myocardial infarction;
   * Poorly controlled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 100 mmHg)
7. inability to swallow, intestinal obstruction, or other factors affecting drug administration and absorption;
8. known to be allergic to the drug components of this protocol: a history of immunodeficiency, including HIV test positive, or suffering from other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
9. pregnant and lactating women (excluding lactating women who stop breastfeeding), fertile women with positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial and within 7 months after the last dose of study drug;
10. patients who are participating in other studies
11. Have serious concomitant diseases or other conditions that would interfere with the planned treatment of concomitant diseases, or any other condition that would make the patient inappropriate for this study in the opinion of other investigators.

Primary outcomes:
measure: Total pathologic complete response（tPCR）
timeFrame: Estimated 24 months
Secondary outcomes:
measure: breast pathologic complete response(bPCR)
timeFrame: Estimated 24 months
measure: Objective Response Rate (ORR)
timeFrame: Estimated 24 months
measure: Adverse Events and Serious Adverse Events
timeFrame: From informed consent through 28 days following treatment completion
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Hunan Cancer Hospital
name: Ying He, M.D.
role: STUDY_CHAIR
References: