A phase II evaluation of lapatinib (L) and bevacizumab (B) in HER2+ metastatic breast cancer (MBC)

Abstract

1042 Background: In a preclinical HER2+ BC model, combination anti-HER2 and anti-VEGF therapy was more effective than either treatment alone, and increased VEGF expression is associated with worse outcome in HER2+ disease. B plus trastuzumab (T) has shown promising activity in patients (pts) with HER2+ MBC, however the cardiac toxicity of this regimen requires further evaluation. L, an oral dual inhibitor of EGFR and HER2, is approved in combination with capecitabine after T-based therapy for HER2+ MBC. L may have less cardiac toxicity and may be a safer and more effective alternative to T+B. This hypothesis was evaluated in a phase 2 trial of L+B in HER2+ MBC pts. Methods: This 50-patient single-arm study evaluated L (1,500 mg PO daily) plus B (10 mg/kg IV q2wk). The primary endpoint is progression-free survival (PFS) at 12 weeks with 84% power to detect a clinically significant PFS rate of 60%; secondary endpoints include toxicity and response per RECIST. Efficacy was assessed at Week 6, 12, and q12wks thereafter. HER2+ status was locally defined as HER2 FISH amplified or IHC3+. Serial evaluation of circulating tumor and endothelial cells and HER2 extracellular domain was performed. Results: Presently 31 pts are enrolled with a median of 4 prior MBC therapies (range 0–13); 30/31 received prior T (median duration 84 weeks, 14–250 weeks). The most commonly-reported AEs included diarrhea (61%), muscle pain (48%), fatigue (39%), nausea (28%), and emesis (29%). Two grade 2 asymptomatic LVEF decreases and one grade 3 GI hemorrhage were reported. At week 12, 16/21 patients were evaluable for efficacy; 3 pts had a partial response (PR), 10 pts had stable disease (SD), and 3 pts had progressive disease (PD), resulting in a 12-week PFS rate of 62%. At week 24, 5/9 (56%) pts have shown clinical benefit (CR, PR, SD ≥ 24 weeks); 2/2 pts remain in PR after 36 weeks. Conclusions: L+ B is well tolerated and has shown promising activity in heavily pretreated HER2+ MBC pts. Updated results from this ongoing trial will be reported. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline Genentech, GlaxoSmithKline GlaxoSmithKline AstraZeneca, Genentech, Genomic Health, GlaxoSmithKline Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Novarits, Pfizer, Roche, sanofi-aventis