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

Clinical Trial

. 2012 Aug;134(3):1149-59.

doi: 10.1007/s10549-012-2126-1. Epub 2012 Jul 5.

Ahmad Awada, Philipp Harter, Jean Luc Canon, Kurt Possinger, Marcus Schmidt, Jacques De Grève, Patrick Neven, Luc Dirix, Walter Jonat, Matthias W Beckmann, Jochen Schütte, Peter A Fasching, Nina Gottschalk, Tatiana Besse-Hammer, Frank Fleischer, Sven Wind, Martina Uttenreuther-Fischer, Martine Piccart, Nadia Harbeck

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Clinical Trial

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

Martin Schuler et al. Breast Cancer Res Treat. 2012 Aug.

Abstract

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 ≥4 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 ≥4 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.

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Figures

Fig. 1

Fig. 1

Kaplan–Meier curves for progression-free survival (treated set)

Fig. 2

Fig. 2

Hazard ratio (95 % CI) of progression-free survival by baseline characteristics for Cohort A. EGFR epidermal growth factor receptor, IHC immunohistochemistry

Fig. 3

Fig. 3

Predose afatinib plasma concentrations at steady state (50 mg). HER human epidermal growth factor receptor, HR hormone receptor

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