title: A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer.
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.
authors: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: Martin
authors: M
authors: Schuler
authors: Ahmad
authors: A
authors: Awada
authors: Philipp
authors: P
authors: Harter
authors: Jean Luc
authors: JL
authors: Canon
authors: Kurt
authors: K
authors: Possinger
authors: Marcus
authors: M
authors: Schmidt
authors: Jacques
authors: J
authors: De Grève
authors: Patrick
authors: P
authors: Neven
authors: Luc
authors: L
authors: Dirix
authors: Walter
authors: W
authors: Jonat
authors: Matthias W
authors: MW
authors: Beckmann
authors: Jochen
authors: J
authors: Schütte
authors: Peter A
authors: PA
authors: Fasching
authors: Nina
authors: N
authors: Gottschalk
authors: Tatiana
authors: T
authors: Besse-Hammer
authors: Frank
authors: F
authors: Fleischer
authors: Sven
authors: S
authors: Wind
authors: Martina
authors: M
authors: Uttenreuther-Fischer
authors: Martine
authors: M
authors: Piccart
authors: Nadia
authors: N
authors: Harbeck
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency* / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077716:Afatinib; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases