Abstract OT3-01-01: A single-arm confirmatory study to evaluate the efficacy of non-surgical therapy for HER2 positive early breast cancer with clinical complete response after primary systemic therapy: (JCOG1806)
Authors: Fujisawa Tomomi , Shigematsu Hideo , Shien Tadahiko , Iwata Hiroji , Sasaki Keita , Shibata Taro 
Published: March 2023

Abstract
Background: The surgical treatment is the standard therapy for early breast cancer (EBC) after primary systemic therapy (PST). In more than half of HER2 positive (HER2(+)) breast cancer, pathological complete response (pCR) is achieved by PST with HER2 inhibitors and chemotherapy. However, non-surgical therapy is not an option for EBC with cCR after PST because of little evidence. We planned a single-arm confirmatory study to evaluate the efficacy and safety of the non-surgical therapy for HER2(+) EBC with cCR after PST. Methods: The key eligibility criteria are as follows: 1) Histologically confirmed as invasive ductal carcinoma of the breast, HER2(+). 2) cT1-2, N0, M0 (UICC 8th). 3) No ipsilateral BC. 4) Women aged 20-74 years. 5) ECOG performance status 0 or 1. 6) Adequate hematologic and organ function. 7) Ejection fraction as cardiac function is over 50%. 8) Written informed consent. HER2 inhibitors (trastuzumab and pertuzumab) and cytotoxic drugs as PST are administered to all patients (pts). After completion of PST, cCR is diagnosed by breast imaging and physical examination. cCR is defined as 1) Not palpable breast mass by physical examination, 2) No enhanced breast mass by enhanced MRI, and 3) No breast mass by ultrasonography. 4) For hormonal receptor (+) EBC, needle biopsy after PST must be done to evaluate the pCR. After a diagnosis of cCR, conventional radiotherapy for whole breast and boost radiation for tumor bed is mandatory, followed by pertuzumab and trastuzumab every 3 weeks for 9 months. In non-cCR cases, surgical resection is performed and adjuvant therapy is not specified. The primary endpoint is a distant metastasis-free survival (DMFS) at 3 years, the secondary endpoints are DFS, OS, RFS, the proportion of local recurrence, and cosmetics outcome. Given that the threshold and expected DMFS at 3-year is 93% and 98% with a significance level of 2.5% (one-sided) and 80% power, 170 cCR cases are required. Assuming half of the HER2 pts reach cCR, 350 pts are required as the sample size started PST. Enrollment launched in January 2020, and 260 pts are enrolled as of July 12, 2022. This clinical trial has been registered at the Japan Registry of Clinical Trials as jRCTs031190129 and conducted by the Japan Clinical Oncology Group (JCOG) Breast Cancer Study Group under a public fund (National Cancer Center Research and Development Fund).
Citation Format: Tomomi Fujisawa, Hideo Shigematsu, Tadahiko Shien, Hiroji Iwata, Keita Sasaki, Taro Shibata. A single-arm confirmatory study to evaluate the efficacy of non-surgical therapy for HER2 positive early breast cancer with clinical complete response after primary systemic therapy: (JCOG1806) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-01-01.