Dual HER2 Blockade/Chemo Improves Outcomes in Older Breast Cancer Patients

The addition of metronomic chemotherapy to dual HER2 blockade increased progression-free survival (PFS) by 7 months compared with HER2 blockade alone in older and frail patients with HER2-positive metastatic breast cancer, according to a new study.

“Despite the high incidence of cancer and its related mortality in the older population, our knowledge about aging and cancer and about optimal treatment for older patients is far from adequate,” wrote study authors led by Hans Wildiers, PhD, of the department of oncology at KU Leuven in Belgium. They conducted a phase II study comparing dual HER2 blockade with trastuzumab and pertuzumab vs that regimen plus metronomic chemotherapy-referring to a regular interval without prolonged breaks at lower doses than normal-with cyclophosphamide.

The study included 80 patients from 8 European countries (41 with chemotherapy, 39 without); all patients had HER2-positive metastatic disease, and had not previously been treated with chemotherapy for metastatic breast cancer. The patients were either 70 years or older or 60 years or older with confirmed functional restrictions; all had a potential frailty profile according to a geriatric screening score. Patients were followed for a median of 20.7 months; the results of the study were published in Lancet Oncology.

At 6 months, the estimated PFS rate was 46.2% among the patients who received dual blockade alone, and 73.4% with the addition of chemotherapy, for a hazard ratio (HR) of 0.65 (95% CI, 0.37–1.12; P = .12). The difference of 27.2% met the threshold required by the study’s protocol for the primary hypothesis, as the study design was not powered for a direct treatment comparison.

The median PFS was 5.6 months with no chemotherapy, and 12.7 months with chemotherapy. At 1 year, the overall survival rate was 67.3% without chemotherapy and 83.8% with chemotherapy, for an HR of 0.92 (95% CI, 0.44–1.91; P = .83). Breast cancer–specific survival was also similar at 1 year between the two groups. Of the deaths in the dual blockade–alone group, 60% were due to breast cancer progression; of those in the chemotherapy group, 71% were due to breast cancer progression.

The investigators wrote that the safety profile of metronomic cyclophosphamide along with dual blockade was acceptable. The most common grade 3/4 adverse events included hypertension (12% chemotherapy group, 15% dual blockade–alone group), diarrhea (12% and 10%, respectively), and dyspnea (10% and 5%, respectively); 10% of chemotherapy patients had a grade 3/4 thromboembolic event, compared with none in the dual blockade–alone group.

“Trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population,” the authors concluded.