Management of antiangiogenics’ renovascular safety in breast cancer subgroup and intermediate results of the MARS study.

Abstract

1095 Background: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of AVD in the clinical setting. Methods: The MARS study is a multicentric prospective observational study of the renovascular safety of AVD in AVD-naive pts. 7 centres from 2009 to 2011. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and Pu. This sub-group analysis presents the intermediate results for the 1st 155 pts with breast cancer (BC) receiving bevacizumab who completed the 1-year follow-up (f/u) (out of 337 BC pts in total). Results: Median age at inclusion: 62 years. Bone, visceral and cerebral metastasis frequencies were 74.2, 51.6 and 5.2%, respectively. Diabetes and HTN prevalences were 3.9% and 10.3%, respectively. Baseline renal assessment retrieved: Pu 14.2%, Hu 8.4%, aMDRD 98.2 ml/min/1.73m2 and 2 pts with aMDRD<60. The incidence of de novo Pu during f/u was 15% (Table). 59.1% of pts with Pu at inclusion improved. Among pts with de novo Pu, 40.0% afterwards improved/normalized. No grade 3/4 Pu has been reported and no hematuria. 12.9% developed HTN. Moreover, renal function decreased by -3.2 ml/min/1.73m2/year and 4 pts had aMDRD<60 at the end of f/u. 32.2% increased their SCr: 27.1% grade 1, 4.5% grade 2, and 0.6% grade 3. All pts with grade 2-3 returned to normal or grade 1. No thrombotic micro-angiopathy (TMA) has been reported. Conclusions: These results show that 1) TMA remains rare, 2) Pu developed in 15% of pts, with no grade 3/4, 3) less than 13% developed HTN and 4) renal function was only slightly impaired with transient elevations in SCr. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]