Findings in a phase I trial reported in The Lancet Oncology by Pernas et al indicate activity of the combination of the CXCR4 chemokine receptor antagonist balixafortide plus eribulin in previously treated HER2-negative metastatic breast cancer. The CXCR4–stromal cell-derived factor-1α (SDF-1α) axis is involved in regulating function and trafficking of immune cells and factors in the tumor microenvironment.
In the study, a total of 56 patients from 11 sites in Spain and the U.S. were enrolled between January 2014 and October 2016 and treated with balixafortide and eribulin (Halaven), both by intravenous infusion. Patients had to have evidence of tumor cell CXCR4 expression and had previously received 1 to 3 chemotherapy regimens for metastatic disease and at least one endocrine therapy if they had hormone receptor–positive disease and were considered suitable for endocrine therapy.
Toxicity and Responses
During the dose-escalation phase of the study, no dose-limiting toxicities were observed and maximum tolerated dose was not reached. The highest dose was established as eribulin 1.4 mg/m² on days 2 and 9 plus balixafortide 5.5 mg/kg on days 1 to 3 and 8 to 10 of 21-day cycles.
Objective response was observed in 16 (30%) of 54 evaluable patients, with stable disease observed in an additional 25 (46%). Median duration of response was 97 days.
The most common adverse events of any grade were fatigue (79%), neutropenia (57%), infusion-related reactions (48%), alopecia (46%), constipation (46%), and nausea (45%). The most common grade 3 or 4 adverse events were neutropenia (41%) and febrile neutropenia (11%). Serious adverse events occurred in 38% of patients, including febrile neutropenia in 9%, urinary tract infection in 5%, decreased neutrophils in 4%, constipation in 4%, and pneumonia in 4%. Two patients (4%) died while receiving study treatment. One patient died from septic shock after developing neutropenia and streptococcal pneumonia. One patient died from pneumonia after developing grade 4 neutropenia.
The investigators concluded, “The safety and tolerability of balixafortide plus eribulin seems to be similar to that of eribulin or balixafortide monotherapy, and the preliminary activity of the combination seems promising in patients with HER2-negative metastatic breast cancer. The results suggest that balixafortide plus eribulin has potential to provide a new therapeutic option in heavily pretreated patients with metastatic breast cancer and warrants further investigation in randomised trials.”
The study was funded by Polyphor.
Javier Cortes, MD, of the Breast Cancer Unit and Gynaecological Tumours, Ramon y Cajal University Hospital, Madrid, is the corresponding author for The Lancet Oncology article.
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