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)

1045 Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown synergistic effect with anti-HER2 therapy on hormone receptor (HR)-positive and HER2-positive breast cancer from preclinical models and several clinical studies, while data of this combination in HR-negative and HER2-positive diseases are limited so far. DAP-HER-01 (NCT04293276) was aimed at evaluate the efficacy and safety of the novel dual-oral, chemotherapy-free regimen of CDK4/6 inhibitor dalpiciclib and pan-HER tyrosine kinase inhibitor pyrotinib in HER2-positive advanced breast cancer (ABC) regardless of HR status, and reported to meet the primary endpoints previously (overall ORR 70%), in which HR-negative patients achieved a higher ORR (81.8%, vs 55.6% in HR-positive patients; Min Yan, et al. ESMO 2021, Poster 276P). Here we reported the updated results of this trial. Methods: DAP-HER-01 was a single-arm, phase 2 study conducted in HER2-positive ABC patients with no more than one prior systemic treatment at advanced setting. Enrolled patients received dalpiciclib and pyrotinib until progression, unaccepted toxicity, or no further benefit. The primary endpoint was ORR as per RECIST 1.1, and secondary endpoints included progression-free survival (PFS), overall survival and safety. Results: Between April 9, 2020, and May 19, 2021, 41 patients were enrolled and received study treatment, and 40 of them were assessable for efficacy. With a median follow-up of 19.2 months, the median progression-free survival (PFS) was 11.0 months (95% CI 7.3-19.3). Considering HR status, the PFS in HR-negative patients was not matured (estimated median: 16.6 months; 95% CI: 7.3- NA), but still showed a tendency to be longer than that in HR-positive patients (median: 9.1 months; 95% CI: 5.4-11.0). Patients with brain metastases at baseline could also benefit from this treatment (median PFS: 11.0; 95% CI: 5.4-NA). Consistent with the safety data reported before, the most common grade 3 or 4 treatment-related adverse events were leukopenia (68.3%), neutropenia (65.9%) and diarrhea (19.5%). Most adverse events were tolerable, and no study-related death reported. Conclusions: Combined with previous reports, our findings suggest dalpiciclib combined with pyrotinib achieved promising efficacy and manageable toxicity in the treatment of HER2-positive ABC, including patients with HR-negative disease or brain metastases. This combination could be considered as a completely oral, chemo-free regimen for patients with HER2-positive ABC and is worthy of further study. Clinical trial information: NCT04293276 .