Abstract P2-13-31: Pyrotinib in combination with docetaxel as first-line treatment for HER2-positive metastatic breast cancer (PANDORA): A single-arm, multicenter phase 2 trial
Authors: Wang Xiaojia , Huang Jian , Zheng Yabing , Shao Xiying , Cao Wenming , Chen Zhanhong , Shi Yanxia , Cai Li , Chen Wenyan , Guo Zhen , Liu Jian , Shen Peng , Chen Yiding , Wang Xian , Li Huiping , Li Man 
Published: March 2022

Abstract
Background: Human epidermal growth factor receptor 2 (HER2) targeted therapy in combination with chemotherapy is the recommended first-line strategy for HER2-positive metastatic breast cancer. Pyrotinib is a small molecule tyrosine kinase inhibitor targeting HER1, HER2, and HER4. The phase 3 PHOEBE trial has proved its superiority over lapatinib when in combination with capecitabine in previously treated, HER2-positive metastatic breast cancer. This phase 2 trial aimed to investigate the activity of pyrotinib plus docetaxel as first-line treatment in HER2-positive metastatic breast cancer. Methods: Patients with measurable disease received oral pyrotinib 400 mg once daily until disease progression or intolerable toxicity. Intravenous docetaxel was given at 75 mg/m2 on day 1 for at least six 21-day cycles. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST 1.1. As per Simon’s optimal two-stage design, if 18 or more of 27 patients achieved complete response (CR) or partial response (PR) in the first stage, additional 40 patients would be enrolled. If 47 or more of 67 patients achieved CR or PR, the study was deemed successful. Considering a dropout rate of 15%, 79 patients were needed. The study is registered with ClinicalTrials.gov, NCT03876587. Results: Between June 2019 and June 2021, a total of 79 patients enrolled and received study treatment. As of June 18, 2021, 14 patients had not undergone response evaluation or had unconfirmed response, while 65 patients were included in the full analysis set. There were two patients meeting the exclusion criteria, leaving 63 patients in the per-protocol set. Of 65 patients, the median age was 52 years (range, 28-70). Most of them had Eastern Cooperative Oncology Group performance status of 1 (69.2%), visceral metastases (56.9%), hormone receptor-positive disease (55.4%), and prior (neo)adjuvant therapy with (27.7%) or without trastuzumab (32.3%). In the first stage, 24 of 27 patients achieved confirmed objective response (one CR and 23 PR), and the study proceeded to the second stage. The confirmed ORR in 65 patients was 78.5% (95% CI, 66.5%-87.7%); two patients achieved CR and 49 achieved PR. The confirmed ORR in the per-protocol set (n=63) was 81.0% (95% CI, 69.1%-89.8%). Progression-free survival was immature. Of 65 patients, the most common grade ≥3 treatment-emergent. adverse events included decreased neutrophil count (30.8%), decreased white blood cell count (26.2%), diarrhea (20.0%), and hypokalemia (6.2%). Grade ≥3 diarrhea was less common in patients with loperamide prophylaxis (5.3%; 2/38) than in those without loperamide prophylaxis (40.7%; 11/27). Conclusions: Pyrotinib in combination with docetaxel exhibits promising antitumor activity and acceptable safety profile among patients with HER2-positive metastatic breast cancer in the first-line setting. Loperamide prophylaxis is an effective approach for the prevention of diarrhea.
Citation Format: Xiaojia Wang, Jian Huang, Yabing Zheng, Xiying Shao, Wenming Cao, Zhanhong Chen, Yanxia Shi, Li Cai, Wenyan Chen, Zhen Guo, Jian Liu, Peng Shen, Yiding Chen, Xian Wang, Huiping Li, Man Li. Pyrotinib in combination with docetaxel as first-line treatment for HER2-positive metastatic breast cancer (PANDORA): A single-arm, multicenter phase 2 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-31.