Dual HER2 blockade with metronomic chemotherapy may be effective for treating elderly patients with HER2-positive metastatic breast cancer, according to a study published in The Lancet Oncology.1

If untreated, HER2-positive metastatic disease can progress quickly. Elderly patients are, furthermore, not well-represented in clinical trials, and the optimal treatments for this patient-group are not yet established.

For this randomized phase 2 trial (ClinicalTrials.gov Identifier: NCT01597414), researchers evaluated whether dual HER2 inhibition with trastuzumab and pertuzumab plus metronomic cyclophosphamide is superior to dual HER2 inhibition alone among elderly patients with HER2-positive metastatic disease. The primary endpoint was the 6-month progression-free survival (PFS) rate.

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Eighty patients were enrolled. Thirty-nine were randomly assigned to the dual inhibition group; 41 were assigned to the chemotherapy group. All patients were at least 60 years old; patients younger than 70 also had “confirmed functional restrictions defined by protocol, and had a life expectancy of more than 12 weeks and a performance status according to WHO [World Health Organization] scale of 0–3.”

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Forty-four percent of patients in the dual HER2 inhibition group and 53% of patients in the chemotherapy group had an overall response; 1 complete response was noted in each group. The estimated 6-month PFS was 46.2% with trastuzumab and pertuzumab vs 73.4% with dual HER2 inhibition plus chemotherapy (hazard ratio, 0.65; P = .12).

At 20.7 months’ follow-up, the median PFS was 5.6 months in the dual inhibition group vs 12.7 months in the chemotherapy group.

Grade 3 to 4 adverse events observed in the dual inhibition and chemotherapy groups included hypertension (15% vs 12%, respectively), diarrhea (10% vs 12%), and a thromboembolic event (0% vs 10%). Four patients in the dual inhibition group died without disease progression; 1 death was due to cardiac arrest during therapy. One patient in the chemotherapy group died after heart failure.

The authors concluded that “dual blockade of HER2 plus metronomic chemotherapy seems to provide a better prognosis than HER2 dual blockade alone in an older and frail population with HER2-positive metastatic breast cancer, and has an acceptable safety profile.”


  1. Wildiers H, Tryfonidis K, Dal Lago, L, et al. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4 [Epub ahead of print]