Abstract 276P
Background
Given nearly all patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) developed resistance to trastuzumab eventually, novel approaches were urgently needed. This study aimed to evaluate the efficacy and safety of a novel CDK4/6 inhibitor dalpiciclib combined with pyrotinib, a HER2-targeted tyrosine kinase inhibitor (TKI), in HER2+ advanced BC.
Methods
In the single-arm, phase II study, HER2+ advanced BC pts who had received no more than 1 line of systemic therapy in advanced setting were recruited. Prior CDK4/6 inhibitors and HER2 targeted TKI were not allowed. Eligible pts received dalpiciclib 125 mg daily for 3 weeks and 1 week off, and pyrotinib 400 mg daily in 28-day cycles. The primary endpoint was objective response rate (ORR) as per RECIST 1.1. Using a 2-stage design, response in at least 13 of the first 23 pts allowed continued enrollment to a planned 41.
Results
24 pts were enrolled in the first stage: HR+ disease, 54.2% (13/24); trastuzumab (tras)-treated, 66.7% (16/24); visceral metastasis, 91.6% (22/24). As of April 13th, 2021, of 23 evaluable pts 65.2% (15/23) had achieved confirmed ORR (15PR, 6SD, 2PD). Descriptive subgroup analyses of ORR were performed based on HR status (100% in HR- pts vs 38.5% in HR+ pts), previous lines of systemic therapy in advanced setting (69.2% in 0 line pts vs 60.0% in 1st-line pts) and resistance to trastuzumab (66.7% in tras-sensitive pts vs 63.6% in tras-resistant pts). 62.5% (15/24) of pts experienced grade 3/4 adverse events (AEs), and the common grade 3/4 AEs were neutropenia (13, 54.2%), leukopenia (12, 50%) and diarrhea (2, 8.3%). Most AEs were tolerable, only 1 patient needed dose reduction.
Conclusions
Dalpiciclib combined with pyrotinib was associated with promising efficacy and manageable toxicity, and could be considered as a completely oral, chemo-free regimen for patients with HER2-positive advanced breast cancer. The enrollment of the second stage is ongoing.
Clinical trial identification
NCT04293276.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.