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

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.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1. Trial profile.

Treatment summary and data collection of study participants.

Fig. 2. Exploratory subgroup analyses of pCR by baseline factors.

Data are presented as pCR rate (%) and 95% CI. The black squares indicate the pCR rates following stratifications. pCR pathological complete response, HER2 human epidermal growth factor receptor 2, IHC immunohistochemistry, FISH fluorescence in situ hybridization, ER estrogen receptor, PR progesterone receptor, CI confidence interval. Source data are provided as a Source Data file.

Fig. 3. Ki-67 expression at baseline and surgery.

a Individual data (n = 48). b Mean percentages of Ki-67 expressing tumor cells of each group (n = 48). Statistical analysis was performed by paired two-sided t-test. The Ki-67 expression in 31 out of 79 patients was not assessable due to the lack of detectable tumor cells in the surgical samples (n = 30) or not undergoing surgery (n = 1). For box plots, the center lines are group medians; the upper and lower limits of the box are the 1st and 3rd quartile, and the whiskers show minimum and maximum values. CI confidence interval. Source data are provided as a Source Data file.

Fig. 4. Results of health-related quality of life questionnaires in QLQ-C30 over time.

a Mean scores of global health status and functioning subscales in QLQ-C30. b Mean scores of functioning subscales in QLQ-BR23. QLQ-C30 quality of life questionnaire-core module, QLQ-BR23 quality of life questionnaire-breast cancer module. Source data are provided as a Source Data file.