Combination yields ‘promising PFS outcomes’ in certain patients with breast cancer
Key takeaways:
- Two-thirds of patients experienced no disease progression 6 months after the start of treatment.
- Results showed increased durability among a subset of patients with HER2-positive disease.
SAN ANTONIO — The combination of zanidatamab, palbociclib and fulvestrant yielded promising PFS results among adults with HER2-positive/hormone receptor-positive metastatic breast cancer, findings from a phase 2A study showed.
A primary analysis of the trail’s results — presented at San Antonio Breast Cancer Symposium — revealed a manageable safety profile associated with the treatment regimen, according to study investigators.
“Zanidatamab in combination with palbociclib plus fulvestrant demonstrated promising PFS outcomes with durable responses in this heavily pretreated population,” Santiago Escrivá-de-Romani, MD, a medical oncologist at Vall d’Hebron Institute of Oncology in Spain, said during a presentation.
Background and methodology
There are currently no curative therapies for HER2-positive metastatic breast cancer. Researchers investigated the efficacy and safety of combination treatment with zanidatamab (Zymeworks), palbociclib (Ibrance, Pfizer) and fulvestrant as a potential way of targeting three pathways among patients with HER2-positive, HR-positive metastatic breast cancer.
Patients eligible for the phase 2A study included individuals with HER2-positive and HR-positive, unresectable, locally advanced or metastatic breast cancer with an ECOG performance score of 1 or less who had received prior treatment with trastuzumab, pertuzumab and trastuzumab emtansine, with no prior CDK4/6 inhibitor.
The study population included 51 adults (median age, 54 years) who received 20 mg/kg IV zanidatamab every two weeks plus palbociclib and fulvestrant at standard doses.
PFS rate at 6 months (PFS6) served as the primary endpoint for part 2 of the trial, with other endpoints including median PFS, confirmed objective response rate, disease control rate and duration of response.
Among the 51 patients in the trial, 32 (63%) had HER2-positive disease.
Results, next steps
Researchers reported a median follow-up time of 16.1 months, with 9 patients (18%) remaining on treatment as of the study’s data cutoff date.
Results showed a PFS6 rate of 67% (69% among patients in the HER2-positive subset), and a median PFS of 11.7 months (14.9 months among patients in the HER2-positive subset).
The most common treatment-related adverse events included diarrhea (80%), neutrophil count decrease/neutropenia (59%), nausea (39%), stomatitis (37%), anemia (29%), vomiting (25%) and asthenia (24%).
Researchers reported several grade 3 or higher treatment-related adverse events in two or more patients, including neutrophil count decrease/neutropenia (53%), diarrhea (14%), anemia (10%), thrombocytopenia (6%), hypokalemia (4%) and hypomagnesemia (4%).
Among adverse events of special interest, researchers noted that 6 patients had cardiac events during treatment. Three patients discontinued palbociclib treatment due to an adverse event, whereas 1 patient discontinued zanidatamab and fulvestrant treatment due to an adverse event.
“This combination therapy was well tolerated with an easily manageable safety profile in heavily pretreated patients with HER2-positive/HR-positive metastatic breast cancer,” Escrivá-de-Romani said during a presentation. “These results support further development of this novel chemotherapy-free treatment regimen for heavily pretreated patients with HER2-positive/HR-positive metastatic breast cancer.”
Collapse
Escrivá-de-Romani S, et al. Abstract LB01-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023; San Antonio.