Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer / Niu, Nan; Qiu, Fang; Xu, Qianshi; He, Guijin; Gu, Xi; Guo, Wenbin; Zhang, Dianlong; Li, Zhigao; Zhao, Yi; Li, Yong; Li, Ke; Zhang, Hao; Zhang, Peili; Huang, Yuanxi; Zhang, Gangling; Han, Hongbin; Cai, Zhengang; Li, Pengfei; Xu, Hong; Chen, Guanglei; Xue, Jinqi; Jiang, Xiaofan; Jahromi, Alireza Hamidian; Li, Jinshi; Zhao, Yu; de Faria Castro Fleury, Eduardo; Huo, Shiwen; Li, Huajun; Jerusalem, Guy; Tripodi, Domenico; Liu, Tong; Zheng, Xinyu; Liu, Caigang. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:1(2022). [10.1038/s41467-022-34838-w]

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer

Zhao, Yu;Tripodi, Domenico;
2022

Abstract

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.
2022
Humans; Female; Letrozole; Ki-67 Antigen; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Protein Kinase Inhibitors; Neoadjuvant Therapy; Breast Neoplasms
01 Pubblicazione su rivista::01a Articolo in rivista
A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer / Niu, Nan; Qiu, Fang; Xu, Qianshi; He, Guijin; Gu, Xi; Guo, Wenbin; Zhang, Dianlong; Li, Zhigao; Zhao, Yi; Li, Yong; Li, Ke; Zhang, Hao; Zhang, Peili; Huang, Yuanxi; Zhang, Gangling; Han, Hongbin; Cai, Zhengang; Li, Pengfei; Xu, Hong; Chen, Guanglei; Xue, Jinqi; Jiang, Xiaofan; Jahromi, Alireza Hamidian; Li, Jinshi; Zhao, Yu; de Faria Castro Fleury, Eduardo; Huo, Shiwen; Li, Huajun; Jerusalem, Guy; Tripodi, Domenico; Liu, Tong; Zheng, Xinyu; Liu, Caigang. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:1(2022). [10.1038/s41467-022-34838-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1660640
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