BIBW 2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor, for the treatment of patients with HER2-negative metastatic breast cancer after failure of no more than two prior chemotherapies.

Abstract

1065 Background: BIBW 2992 is a novel, oral, irreversible EGFR/HER1 and HER2 inhibitor. It has preclinical activity in HER2- positive and triple-negative SUM 149-PT xenograft models, and clinical phase I activity. Efficacy and biomarker results of a phase II study of BIBW 2992 in patients with HER2-negative, hormone receptor (HR)-positive or triple-negative breast cancer are presented. Methods: Patients had HER2-negative metastatic breast cancer (MBC), with progression following no more than two prior lines of chemotherapy. No prior EGFR-targeted therapy was allowed. Patients received 50 mg BIBW 2992 once-daily until disease progression. Tumor assessment was performed every other treatment cycle (q 28 days). The primary endpoint was objective response rate (ORR) by RECIST in patients with HER2-negative, HR-positive (cohort A), and clinical benefit for ≥4 cycles in triple-negative (cohort B) MBC. Safety data were collected. Biomarker analyses included HER2, ER, PR, EGFR, CK 5, CK 6, and CK 14 status by IHC. Reflex HER2-FISH was performed where necessary. HER2-ECD and EGFR-ECD were assessed at various time points. Results: Fifty patients received treatment, including 29 patients in cohort A and 21 patients in cohort B. No ORs were observed in either cohort. Median PFS was 53 days and 54 days for cohorts A and B, respectively. Three patients with triple-negative MBC had SD for at least 4 treatment cycles, one of them for 12 cycles (median 184 days; range 132–335 days). The most frequently observed BIBW 2992-related side-effects were gastrointestinal and skin- related adverse events, which were manageable by symptomatic treatment and dose reductions. BIBW 2992 pharmacokinetics appear similar to those observed in previously reported phase I trials. Biomarker analyses are currently ongoing. Conclusions: Long-term oral administration of BIBW 2992 was safe in HER2-negative MBC patients. Side-effects mainly affected the skin and gastrointestinal tract, and were manageable. Clinical benefit was achieved in a fraction of triple-negative MBC patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim