Neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer: A pilot trial.

person Jinqi Xue Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China info_outline Jinqi Xue, Nan Niu, Shuo Wang, Guanglei Chen, Fang Qiu, Yi Zhao, Fei Xing, Xinyu Zheng, Wei Tu, Ke Li, Hai Zhao, Meiyue Tang, Qianshi Xu, Chao Liu, Yafei Zhao, Xiaofan Jiang, Shiwen Huo, Zheng Pang, Dianlong Zhang, Caigang Liu

Authors person Jinqi Xue Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China info_outline Jinqi Xue, Nan Niu, Shuo Wang, Guanglei Chen, Fang Qiu, Yi Zhao, Fei Xing, Xinyu Zheng, Wei Tu, Ke Li, Hai Zhao, Meiyue Tang, Qianshi Xu, Chao Liu, Yafei Zhao, Xiaofan Jiang, Shiwen Huo, Zheng Pang, Dianlong Zhang, Caigang Liu Organizations Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China, Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China, Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China, Department of Breast Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, China, Department of Breast Surgery, Anshan Cancer Hospital, Anshan, China, Department of Breast Surgery, Fushun Cancer Hospital, Fushun, China, Jiangsu Hengrui Pharmaceuticals Co.,Ltd, Shanghai, China, Department of Breast and Throid Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Jiangsu Hengrui Pharmaceuticals Co., Ltd., Outstanding Young Scholars of Liaoning Province (2019-YQ-10), Outstanding Scientific Fund of Shengjing Hospital (201803) Background: Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib plus dalpiciclib (cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with triple-positive breast cancer (TPBC), but the efficacy still needs improvement. This pilot study explored the efficacy and safety of adding trastuzumab to this neoadjuvant regimen in TPBC. Methods: Patients received five 28-day cycles of pyrotinib (320 mg once daily), dalpiciclib (125 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), followed by surgery. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, residual cancer burden (RCB), change in Ki-67 level from baseline to surgery, and safety. Results: Between February 16, 2022 and June 2, 2022, 12 patients were enrolled. Seven (58%; 95% CI, 27.7-84.8) patients achieved tpCR and bpCR. The rate of RCB 0-I was 75% (95% CI, 46.8-91.1%). ORR was 92% (95% CI, 64.6-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5% - 70.5%) at baseline to 17.2% (95% CI, 0.7% - 33.7%) after neoadjuvant therapy (P<0.05). The most common grade 3 adverse events were diarrhea (4 [33%]) and decreased neutrophil count (3 [25%]). No grade 4 events or treatment-related deaths occurred. Conclusions: This four-drug neoadjuvant regimen shows promising pathological response in patients with TPBC, with an acceptable safety profile. The results warranted further validation. Clinical trial information: NCT05228951.