Study Identifies Triplet Combination for Heavily Pretreated HER2+ Breast Cancer

The addition of tucatinib to trastuzumab and capecitabine better improved overall survival (OS) and progression-free survival (PFS; primary endpoint) compared with the addition of placebo in women with human epidermal growth factor receptor 2-positive metastatic breast cancer, according to a study published in The New England Journal of Medicine.

Patients previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine were randomized to receive tucatinib or placebo in combination with trastuzumab and capecitabine.

Improved survival with the addition of tucatinib

PFS at one year was 33.1% in the tucatinib, trastuzumab, and capecitabine group and 12.3% in the placebo group (hazard ratio [HR], 0.54; 95% CI, 0.42-0.71; P<0.001). Median duration of PFS was 7.8 months and 5.6 months, respectively.

Two-year OS was 44.9% in the trastuzumab, pertuzumab, and trastuzumab arm and 26.6% in the placebo cohort (HR, 0.66; 95% CI, 0.50-0.88; P=0.005), and median OS was 21.9 months and 17.4 months, respectively.

The triplet combination also improved survival in a cohort of women with brain metastases: One-year PFS in this cohort was 24.9% with tucatinib, trastuzumab, and capecitabine versus 0% in the placebo group (HR, 0.48; 95% CI, 0.34-0.69; P<0.001). Median PFS was 7.6 months and 5.4 months, respectively.

Common adverse events associated with the tucatinib, trastuzumab, and capecitabine cohort included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. The researchers noted that the risks of diarrhea and elevated aminotransferase levels were particularly higher with the addition of tucatinib.