Chemotherapy-Free Combination Regimen in HER2-Positive Breast Cancer
Luca Gianni, MD, of the Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy, and colleagues reported that a combined drug regimen targeting estrogen receptor (ER), HER2, and RB1 pathways in patients with HER2-positive, ER-positive breast cancer may prove to be an effective chemotherapy-free treatment strategy. It also showed a significant effect on the expression of Ki67 at 2 weeks and at surgery after 16 weeks of treatment, with only clinically minor adverse events reported. These study findings, which support further investigation in larger cohorts of women, were published in The Lancet Oncology.
The four-drug regimen was administered to 35 patients with previously untreated HER2-positive, ER-positive breast cancer. Trastuzumab and pertuzumab were both administered intravenously. Palbociclib was given orally, and fulvestrant was delivered intramuscularly. The co-primary endpoints were Ki67 changes from baseline at 2 weeks after starting the regimen and at surgery and changes in apoptosis from baseline to surgery.
The geometric mean Ki67 expression was 31.9 at baseline, compared with 4.3 at week 2 and 12.1 at the time of surgery. The geometric mean for apoptosis was 1.2 at baseline, compared with 0.4 at the time of surgery. Nearly all patients (97%) had a clinical objective response immediately before surgery. Neutropenia and diarrhea were the most frequent grade 3 adverse events reported, and no grade 4 or serious adverse events were recorded.