Cardiovascular safety of adjuvant bevacizumab for breast cancer.

Abstract

571 Background: Limited data describe the cardiovascular safety of bevacizumab (B) exposure after anthracycline-based adjuvant chemotherapy. We sought to examine rates of cardiovascular dysfunction during and following treatment with adjuvant B for breast cancer. Methods: DFCI 05-055 was a phase II pilot study for patients (pts) with residual invasive carcinoma following neoadjuvant chemotherapy for stage II-III breast cancer. Four sequential 40 pt cohorts were treated with B 15 mg/kg every 3 weeks for 12 months (mo) as monotherapy, with metronomic chemotherapy for 6 mo, with capecitabine 14 day (d) on/7d off for 18 weeks, or 7d on/7d off for 6 mo. Concurrent endocrine and/or trastuzumab therapy was allowed. The primary endpoint was feasibility and tolerability of the combination therapy. Pts underwent cardiac evaluation by MUGA at baseline and 6 mo; a small subset also had MUGA 1 year after completing B. Blood pressure was monitored at each visit and toxicity was graded per CTCAE v.3. Results: 163 pts (median age 51, range 28-77) were treated; of those, 95% had prior neoadjuvant anthracycline, and 10% received prior and concurrent trastuzumab. All treated pts had baseline MUGA, median LVEF 62% (range 51-80). At 6 mo, median LVEF was 62% (range 45-75); 11 pts experienced a drop in LVEF of 10-14%, and 2 pts ≥ 15%. 4 pts (2.4%) had changes in LVEF leading to cessation of protocol therapy; 2 with grade 2 LVEF detected at the 6 month MUGA, and 2 with symptomatic grade 3/4 LVEF detected at 4 and 11 months. All 4 had prior anthracycline exposure, and one was also receiving concurrent trastuzumab. 3 pts recovered LVEF to normal range; 1 pt with history of mantle RT for lymphoma died of progressive CHF. 16 pts underwent MUGA 1 year after completing B; median LVEF was 61% (range 53-77%). Grade 3 hypertension (HTN) was observed in 13 pts (8%); 3 ceased protocol therapy due to HTN. Conclusions: Adjuvant B may be associated with cardiovascular toxicity including hypertension, modest changes in ejection fraction, and rare instances of congestive heart failure. Detailed cardiovascular safety assessments are important in ongoing trials of biologics, particularly amongst women with other cardiac risk factors and in those who develop treatment-related hypertension. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech/Roche Genentech/Roche Genentech/Roche