Cutaneous responses in HER2+ metastatic breast cancer: A retrospective case series of a Phase 1b study of Tucatinib, an Oral HER2-specific inhibitor in combination with Capecitabine and/or Trastuzumab in third-line or later treatment

Cutaneous metastases are a common and very morbid development in women with metastatic breast cancer (MBC). Tucatinib, an oral, potent, HER2-specific reversible tyrosine kinase inhibitor, is a new treatment for HER2-positive MBC. Here, we describe a case series of 7 patients who had cutaneous metastases from a phase 1b study of tucatinib. The phase 1b study enrolled women with progressive HER2-positive MBC previously treated with trastuzumab, pertuzumab, and ado-trastuzumab emtansine. Prior lapatinib, neratinib, or afatinib were allowed. Tucatinib was dosed in 2 cohorts of 350 mg (8 patients) and 300 mg (52 patients) orally twice daily with either capecitabine (1000 mg/m2 orally twice daily for 14 days of a 21-day cycle) or trastuzumab (8 mg/kg intravenous load then 6 mg/kg every 21 days) or the triplet. A total of 60 patients were treated, 16 of which (26.7%) had cutaneous metastasis. The experience of seven patients with cutaneous metastasis treated at three participating centers is described here. The seven patients, aged 36 to 58 years, had received a median 6 prior lines of therapy (range: 3-9), including lapatinib (n=6) and pertuzumab (n=6). All patients received tucatinib with an additional therapy (capecitabine or trastuzumab), and 5 patients received triplet therapy. The median time on therapy was 8 cycles (range: 5-12). Complete (n=1) or partial responses (n=3) of skin disease were observed in 4 patients resulting in a cutaneous response rate of 57.1%. An overall response (including all disease sites) was observed in 4 patients (57.1%). Tucatinib shows evidence of efficacy against cutaneous metastasis, which is common and difficult to control for patients with HER2-overexpressing MBC.