medwireNews: Combination therapy with the C-X-C chemokine receptor type 4 (CXCR4) antagonist balixafortide plus eribulin chemotherapy shows potential in heavily pretreated patients with HER2-negative metastatic breast cancer, phase I study data show.
The safety and tolerability of the combined therapy was similar to that of eribulin or balixafortide monotherapy, and around one-third of patients experienced a partial response, Javier Cortes (Ramón y Cajal University Hospital, Madrid, Spain) and colleagues remark.
They say: “The results suggest that balixafortide plus eribulin has potential to provide a new therapeutic option” in this patient group, and the regimen “warrants further investigation in randomised trials.”
The single-arm, dose-escalation trial involved 56 women who had received up to three previous chemotherapy regimens for metastatic breast cancer and at least one endocrine therapy, where appropriate. Tumor cells from all of the women showed evidence of CXCR4 expression.
The first cohort of patients (n=3) received the per-protocol regimen of intravenous eribulin 1.4 mg/m2 on days 2 and 9 of a 21-day cycle and intravenous balixafortide from a starting dose of 1.0 mg/kg with dose increments of 0.5 or 1.0 mg/kg, on days 1–3 and 8–10.
However, a treatment-related fatal adverse event in this cohort led to a protocol amendment allowing the study to be conducted in two parts, with three cohorts (n=9 patients) receiving de-escalated doses of eribulin (1.1–1.4 mg/m2) plus balixafortide (0.5–1.0 mg/kg) to better assess the safety and pharmacokinetics of the combination.
Since this phase did not highlight any dose-limiting toxicities or eribulin–balixafortide interactions, the remaining 44 patients, including 22 in an expansion cohort, received the originally planned regimen starting at a balixafortide dose of 2 mg/kg.
The researchers report that there were no dose-limiting toxicities and the maximum tolerated dose was not reached. Therefore, the highest dose was established as eribulin 1.4 mg/m2 on days 2 and 9, and balixafortide 5.5 mg/kg on days 1–3 and 8–10 of the 21-day cycle.
At 1 year, the estimated overall survival rate was 62%. The objective response rate was 30% in 54 patients who were evaluable for antitumor activity (all partial responses), while the clinical benefit rate was 44%.
Median progression-free survival was 4.6 months overall, and 6.2 months among the 22 patients in the expansion cohort who received the maximum balixafortide dose.
Cortes and co-authors comment that this is “higher than that reported for eribulin alone in any trial with similar patients.”
The most common treatment-emergent adverse events of any grade were fatigue (79%), neutropenia (57%), infusion-related reactions (48%), alopecia (46%), constipation (46%), and nausea (45%).
Serious adverse events were reported in 38% of patients, and included febrile neutropenia (9%), urinary tract infection (5%), neutrophil count decrease (4%), constipation (4%), and pneumonia (4%).
There were two (4%) fatal adverse events overall: the patient in cohort 1 who died of septic shock, and another in the expansion cohort who died of pneumonia following grade 4 neutropenia.
The study findings are published in The Lancet Oncology.
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group