Xiaorong Zhong1,2, Ping He1, Jie Chen3, Xi Yan1, Bin Wei4, Zhang Zhang4, Hong Bu4, Jing Li5, Tinglun Tian1, Qing Lv3, Xiaodong Wang3, Hongjiang Li3, Jing Wang3, Juan Huang6, Jiaojiao Suo1, Xiaoxiao Liu7, Hong Zheng1,2, Ting Luo1,2. 1. Department of Head, Neck, and Mammary Gland Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. 2. Laboratory of Molecular Diagnosis of Cancer, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, China. 3. Department of Pathology, West China Hospital, Sichuan University, Chengdu, China. 4. Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, China. 5. The Chinese Cochrane Center, West China Hospital, Sichuan University, Chengdu, China. 6. Department of Radiology, West China Hospital, Sichuan University, Chengdu, China. 7. Department of Radiation Oncology, Cancer Center, Affiliated Hospital of Xuzhou Medical University, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China.
Abstract
BACKGROUND: The anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC. METHODS: In this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles. RESULTS: Between May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively. CONCLUSIONS: In women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057). 2022 Gland Surgery. All rights reserved.
BACKGROUND: The anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC. METHODS: In this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles. RESULTS: Between May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively. CONCLUSIONS: In women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057). 2022 Gland Surgery. All rights reserved.
Entities:
Keywords:
Neoadjuvant therapy; albumin-bound paclitaxel; human epidermal growth factor receptor 2-positive breast cancer; pyrotinib; trastuzumab
Authors: D J Slamon; B Leyland-Jones; S Shak; H Fuchs; V Paton; A Bajamonde; T Fleming; W Eiermann; J Wolter; M Pegram; J Baselga; L Norton Journal: N Engl J Med Date: 2001-03-15 Impact factor: 91.245
Authors: Evandro de Azambuja; Andrew P Holmes; Martine Piccart-Gebhart; Eileen Holmes; Serena Di Cosimo; Ramona F Swaby; Michael Untch; Christian Jackisch; Istvan Lang; Ian Smith; Frances Boyle; Binghe Xu; Carlos H Barrios; Edith A Perez; Hatem A Azim; Sung-Bae Kim; Sherko Kuemmel; Chiun-Sheng Huang; Peter Vuylsteke; Ruey-Kuen Hsieh; Vera Gorbunova; Alexandru Eniu; Lydia Dreosti; Natalia Tavartkiladze; Richard D Gelber; Holger Eidtmann; José Baselga Journal: Lancet Oncol Date: 2014-08-14 Impact factor: 41.316
Authors: Erin R Gardner; William L Dahut; Charity D Scripture; Jacquin Jones; Jeanny B Aragon-Ching; Neil Desai; Michael J Hawkins; Alex Sparreboom; William D Figg Journal: Clin Cancer Res Date: 2008-07-01 Impact factor: 12.531