According to primary results from a phase 2a study, the addition of zanidatamab, a bispecific HER2-targeted antibody, to standard palbociclib and fulvestrant demonstrated promising progression-free survival (PFS) and durable response among patients with HER2-positive, hormone receptor (HR)-positive, metastatic breast cancer.

“[HER2-positive metastatic breast cancer] remains incurable, thus novel HER2‑directed therapies including chemotherapy-free options are needed,” stated Santiago Escrivá-de-Romani, MD, Vall d’Hebron Institute of Oncology, Barcelona, Spain, and coauthors. Prior results “demonstrated antitumor activity and a tolerable safety profile for [zanidatamab plus palbociclib plus fulvestrant] in heavily pretreated [patients] with [HER2-positive, hormone receptor-positive, metastatic breast cancer].”

In this study, 51 patients with HER2-positive, HR-positive, unresectable, locally advanced or metastatic breast cancer received 200 mg/kg of zanidatamab once every 2 weeks plus palbociclib and fulvestrant. Eligible patients had previously been treated with at least one line of trastuzumab, pertuzumab, and ado-trastuzumab emtansine. Patients previously treated with a CDK4/6 inhibitor were excluded. The primary end point was 6-month PFS. Secondary end points included median PFS, confirmed objective response rate (ORR), disease control rate (DCR), and median duration of response (DOR). 

At a median follow-up of 16.1 months, 6-month PFS was 67% and median PFS was 11.7 months. Confirmed ORR was 34.8%, DCR was 91.3%, and median DOR was 14.8 months. At analysis, 9 patients remained on treatment and the median duration of zanidatamab treatment was 8.4 months. The most common treatment-related adverse events occurring in >20% of patients included diarrhea (80%), neutrophil count decrease/neutropenia (59%), nausea (39%), stomatitis (37%), anemia (29%), vomiting (25%), and asthenia (24%). Grade ≥3 treatment-related adverse events occurring in ≥2 patients included neutrophil count decrease/neutropenia (53%), diarrhea (14%), anemia (10%), thrombocytopenia (6%), hypokalemia (4%), and hypomagnesemia (4%). Patients additionally experienced grade ≤3 cardiac events (n = 6) and grade 1 infusion-related reactions (n = 2). Three patients discontinued palbociclib and 1 patient discontinued zanidatamab and fulvestrant due to an adverse event. No treatment-related deaths were reported. 

“These results support further development of a novel chemotherapy-free treatment regimen for heavily pretreated [patients] with [HER2-positive/HR-positive metastatic breast cancer],” concluded Dr Escrivá-de-Romani and coauthors. 

Source: 

Escrivá-de-Romani S, Cejalvo JM, Alba E, et al. Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC). Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023. San Antonio, Texas. Abstract LBA01-04