Zanidatamab Plus Palbociclib and Fulvestrant Demonstrates Promise in HR-Positive, HER2-Positive Metastatic Breast Cancer
According to results from a phase 2a study, zanidatamab plus palbociclib and fulvestrant demonstrated promising efficacy and safety among previously treated patients with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-positive unresectable or metastatic breast cancer.
“New HER2-targeted regimens, including chemotherapy-free options, are needed for metastatic breast cancer,” stated Santiago Escrivá-de-Romani, MD, Vall d'Hebron University Hospital, Barcelona, Spain, and coauthors. Here, “we assessed the safety and antitumour activity of zanidatamab, a HER2-targeted bispecific antibody, plus palbociclib and fulvestrant, in heavily pretreated patients with hormone receptor-positive, HER2-positive advanced or metastatic breast cancer.”
In this multicenter, single-arm study, researchers enrolled 51 patients with HR-positive, HER2-positive unresectable or metastatic breast cancer who experienced disease progression on or after prior HER2-targeted therapies. Patients received 20 mg/kg of zanidatamab (once every 2 weeks on days 1 and 15 of a 28-day cycle) plus 125 mg of palbociclib (once daily on days 1 through 21 of each cycle) and 500 mg of intramuscular fulvestrant (once every 2 weeks for the first 3 doses, followed by once every 4 weeks). Primary end points included 6-month progression-free survival (PFS) rate and safety.
At a median follow-up of 16.1 months with all patients receiving study treatment at the recommended dose, the median treatment duration was 7.4 months. The 6-month PFS rate was 66.7%. All patients experienced at least 1 treatment-related adverse event of any grade, most frequently diarrhea. Grade 3/4 treatment-related adverse events occurred in 67% of patients, most frequently neutropenia (51%). Serious grade 3 treatment-related transaminases occurred in 1 patient. No treatment-related deaths occurred.
“Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen,” concluded Dr Escrivá-de-Romani et al.
Source:
Escrivá-de-Romani S, Cejalvo JM, Alba E, et al. Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: Primary results from a two-part, multicentre, single-arm, phase 2a study. Lancet Oncol. Published online: May 5, 2025. doi: 10.1016/S1470-2045(25)00140-8
