In 2021, the results of the single-arm, phase 2 DAP-HER-01 study demonstrated promising efficacy and safety with the cyclin-dependent kinase 4/6 inhibitor dalpiciclib plus the pan HER tyrosine kinase inhibitor pyrotinib in patients with HER2-positive advanced breast cancer independent of hormone receptor (HR) status.1
The updated results of the DAP-HER-01 study were reported at the 2023 ASCO annual meeting.2 The DAP-HER-01 study enrolled patients with HER2-positive advanced breast cancer who had received ≤1 previous systemic treatment in the advanced setting. Eligible patients received dalpiciclib and pyrotinib until progression, unacceptable adverse events, or no further benefit. The primary end point was the objective response rate per RECIST version 1.1; the secondary end points included progression-free survival (PFS), overall survival, and safety.
A total of 41 patients were enrolled and received treatment in the study, of whom 40 were evaluable for efficacy. At a median follow-up of 19.2 months, the median PFS in the overall population was 11 months. Although the PFS data are still not mature, the HR-negative cohort showed a trend for longer PFS compared with the HR-positive cohort (16.6 months vs 9.1 months, respectively; 95% confidence interval, 7.3-not achieved vs 5.4-11, respectively). The subgroup with brain metastases at baseline was associated with a median PFS of 11 months.
The most common grade ≥3 treatment-related adverse events were leukopenia (68.3%), neutropenia (65.9%), and diarrhea (19.5%); no treatment-related deaths were reported.
The findings of the DAP-HER-01 trial show that oral, chemotherapy-free dalpiciclib combined with pyrotinib resulted in promising efficacy and manageable adverse events in patients with HER2-positive advanced breast cancer, including in those with HR-negative disease or brain metastases.
- Yan M, Niu L, Lv H, et al. Dalpiciclib, a novel CDK4/6 inhibitor, combined with pyrotinib for HER2+ advanced breast cancer: interim results of a phase II trial. Abstract presented at: ESMO Congress, September 17-21, 2021; Paris, France. Poster 276P.
- Yan M, Niu L, Lv H, et al. Updated results from a phase 2 study on dalpiciclib and pyrotinib, a dual-oral chemotherapy-free regimen in HER2-positive advanced breast cancer (DAP-HER-01). Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract 1045.