A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer

作者：Schuler Martin; Awada Ahmad; Harter Philipp; Canon Jean Luc; Possinger Kurt; Schmidt Marcus; De Greve Jacques; Neven Patrick; Dirix Luc; Jonat Walter; Beckmann Matthias W; Schuette Jochen; Fasching Peter A; Gottschalk Nina; Besse Hammer Tatiana; Fleischer Frank; Wind Sven; Uttenreuther Fischer Martina; Piccart Martine; Harbeck Nadia^*

来源：Breast Cancer Research and Treatment, 2012, 134(3): 1149-1159.

DOI：10.1007/s10549-012-2126-1

• Afatinib
• Metastatic breast cancer
• Triple-negative breast cancer
• HER2-negative breast cancer
• EGFR TKI

Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits signaling from all relevant ErbB-family dimers. Afatinib has demonstrated preclinical activity in human epidermal growth factor receptor HER2 (ErbB2)-positive and triple-negative xenograft models of breast cancer, and clinical activity in phase I studies. This was a multicenter phase II study enrolling patients with HER2-negative metastatic breast cancer progressing following no more than three lines of chemotherapy. No prior epidermal growth factor receptor-targeted therapy was allowed. Patients received 50-mg afatinib once daily until disease progression. Tumor assessment was performed at every other 28-day treatment course. The primary endpoint was clinical benefit (CB) for a parts per thousand yen4 treatment courses in triple-negative (Cohort A) metastatic breast cancer (TNBC) and objective responses measured by Response Evaluation Criteria in Solid Tumors in patients with HER2-negative, estrogen receptor-positive, and/or progesterone receptor-positive breast cancer (Cohort B). Fifty patients received treatment, including 29 patients in Cohort A and 21 patients in Cohort B. No objective responses were observed in either cohort. Median progression-free survival was 7.4 and 7.7 weeks in Cohorts A and B, respectively. Three patients with TNBC had stable disease for a parts per thousand yen4 treatment courses, one of them for 12 courses (median 26.3 weeks; range 18.9-47.9 weeks). The most frequently observed afatinib-associated adverse events (AEs) were gastrointestinal and skin-related side effects, which were manageable by symptomatic treatment and dose reductions. Afatinib pharmacokinetics were comparable to those observed in previously reported phase I trials. In conclusion, afatinib had limited activity in HER2-negative breast cancer. AEs were generally manageable and mainly affected the skin and the gastrointestinal tract.

• 出版日期2012-8