Use of Metronomic Chemotherapy in Older Patients With Metastatic Breast Cancer
Posted: Thursday, April 26, 2018
The addition of metronomic oral cyclophosphamide to trastuzumab plus pertuzumab may increase progression-free survival in older and frail patients with HER2-positive metastatic breast cancer compared with dual anti-HER2 therapy alone, according to the results of a trial from the Elderly Task Force/Breast Cancer Group published in The Lancet Oncology. Metronomic chemotherapy refers to treatment at regular, close intervals without prolonged breaks at doses substantially lower than the maximum tolerated dose.
“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti-HER2 blockade alone does not compensate for the substantial loss of activity in the metastatic breast cancer setting,” noted Hans Wildiers, MD, PhD, of the University Hospitals Leuven, Belgium, and colleagues.
The multicenter, phase II trial included 80 women 70 years and older, or 60 years and older with functional restrictions. They had HER2-positive metastatic breast cancer without previous chemotherapy for metastatic disease. Patients were randomized to receive metronomic oral cyclophosphamide at 50 mg/day plus trastuzumab and pertuzumab (n = 41) or trastuzumab and pertuzumab alone (n = 39). In the case of disease progression, all patients were offered ado-trastuzumab emtansine.
Progression-free survival at 6 months was 73.4% in the metronomic chemotherapy group versus 46.2% in the control group (hazard ratio = 0.65, P = .12). Although this difference was not found to be statistically significant, the study was not powered for a direct treatment comparison. At a median follow-up of 20.7 months, the median progression-free survival was 12.7 months with metronomic chemotherapy versus 5.6 months without. Both arms had a similar safety profile, with grade 3 and 4 adverse events including hypertension, diarrhea, and fatigue.