Multicenter phase 2 trial of palbociclib, fulvestrant, trastuzumab, and pyrotinib for breast cancer with brain metastases

Patients with HR-positive/HER2-positive advanced breast cancer (HR+ HER2+ ABC) face a high risk of brain metastases (BMs), yet prospective systemic-treatment evidence for this group is limited. A multicenter phase 2 trial in China evaluated a chemotherapy-sparing regimen of palbociclib, fulvestrant, trastuzumab, and pyrotinib for patients with HR+ HER2+ ABC and measurable BMs who had no prior local treatment to the target lesion. The regimen was administered until progression or unacceptable toxicity. The primary endpoint was confirmed central nervous system objective response (CNS-ORR). A total of 32 patients were enrolled. Among 29 response-evaluable patients, the confirmed CNS-ORR was 58.6% (95% CI 40.7-74.5) while the overall ORR was 62.1% (44.0-77.3). With median follow-up of 32.5 months, median CNS-PFS was 9.6 months (95% CI 5.3-13.9) and median overall PFS was 12.3 months (6.8-17.7). Overall survival data were immature with 5 deaths (24-months OS rate 80.7%). Post-hoc analysese suggested numerically better PFS and CNS-PFS in chemotherapy-naïve patients, whereas prior trastuzumab did not impair efficacy. Frequent grade 3 or 4 adverse events were diarrhea (37.5% of patients), neutropenia (28.1%), and leukopenia (15.6%) with no treatment-related deaths. The authors conclude that this chemotherapy-sparing quadruple regimen showed promising intracranial activity, systemic disease control, and manageable toxicity among HR+ HER2+ ABC patients with BMs