A pilot study of vascular endothelial growth factor inhibition with bevacizumab in patients with lymphedema following breast cancer treatment

9523 Background: Lymphedema is a significant long-term complication of primary therapy for breast cancer. Anecdotally, several patients (pts) with metastatic disease treated with bevacizumab monotherapy noted improvement in long-standing lymphedema. This pilot study was conducted to explore these observations prospectively. Methods: We used an existing biospecimen bank to conduct a case-control study to compare VEGF-A, -C, -D and VEGFR-3 serum concentrations in breast cancer pts with and without lymphedema (matched for age and LN status). In a separate pilot trial, pts with significant unilateral lymphedema receive bevacizumab, 15 mg/kg every 3 weeks. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C, -D, and R3. IFP is measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R3 are assessed at 3 and 6 weeks. Results: Samples were available for 16 pts with chronic lymphedema and 31 matched controls. Median VEGF-C levels were significantly increased in pts with lymphedema (6895 pg/ml vs. 5349 pg/ml, p=0.001). Twelve pts have been enrolled in the pilot trial. Median duration of lymphedema was 6.3 years (0.5–16.6) Median time since surgery was 5.5 years (1.9–17.6); median time since radiation (n=10) was 5.1 years (1.3–8.3). Complete IFP data is available in 9 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (7.63 vs. -0.87 mmHg; p=0.0023). Mean IFP in the affected arm decreased an average of 41.9% 24 hours after bevacizumab infusion (7.63 vs. 4.88 mmHg; p=0.07). ECF, VEGF-1, and VEGF-R3 levels all significantly decreased three weeks after initial treatment. Two patients met the definition of response with a ≥ 25% reduction in excess arm volume though the mean difference in excess arm volume did not significantly change (p=0.19). Conclusions: Preliminary data supports the hypothesis that VEGF plays a central role in the development and persistence of lymphedema after local therapy for breast cancer. Bevacizumab acutely decreases IFP, leading to a decrease in ECF and modest improvement in arm volume. [Table: see text]