title: A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab.
abstract: Afatinib is an oral, ErbB family blocker, which covalently binds and irreversibly blocks all kinase-competent ErbB family members. This phase II, open-label, single-arm study explored afatinib activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients progressing after trastuzumab treatment. Patients had stage IIIB/IV HER2-positive metastatic breast cancer, with progression following trastuzumab or trastuzumab intolerance and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients received 50 mg afatinib once-daily until disease progression. Primary endpoint was objective response rate (Response Evaluation Criteria in Solid Tumors 1.0), with tumor assessments every 8 weeks. Forty-one patients were treated. Patients had received a median of three prior chemotherapy lines (range, 0-15) and 68.3% had received trastuzumab for >1 year. Four patients (10% of 41 treated; 11% of evaluable patients) had partial response. Fifteen patients (37% of 41) had stable disease as best response and 19 (46% of 41) achieved clinical benefit. Median progression-free survival was 15.1 weeks (95% confidence interval [CI]: 8.1-16.7); median overall survival was 61.0 weeks (95% CI: 56.7-not evaluable). Most frequent common terminology criteria for adverse events grade 3 treatment-related adverse events were diarrhea (24.4%) and rash (9.8%). Afatinib monotherapy was associated with promising clinical activity in extensively pretreated HER2-positive breast cancer patients who had progressed following trastuzumab treatment.
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Nancy_Lin@dfci.harvard.edu
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Duncan
authors.initials: D
authors.lastname: Wheatley
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.forename: Stephen
authors.initials: S
authors.lastname: Houston
authors.forename: David
authors.initials: D
authors.lastname: Mendelson
authors.forename: Pamela
authors.initials: P
authors.lastname: Munster
authors.forename: Laurie
authors.initials: L
authors.lastname: Frakes
authors.forename: Steve
authors.initials: S
authors.lastname: Kelly
authors.forename: Agustin A
authors.initials: AA
authors.lastname: Garcia
authors.forename: Susan
authors.initials: S
authors.lastname: Cleator
authors.forename: Martina
authors.initials: M
authors.lastname: Uttenreuther-Fischer
authors.forename: Hilary
authors.initials: H
authors.lastname: Jones
authors.forename: Sven
authors.initials: S
authors.lastname: Wind
authors.forename: Richard
authors.initials: R
authors.lastname: Vinisko
authors.forename: Tamas
authors.initials: T
authors.lastname: Hickish
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000077716:Afatinib; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab