Hypertension (HTN) and proteinuria (PTN) as biomarkers of efficacy in antiangiogenic therapy for metastatic colorectal cancer (mCRC).

Abstract

e13580 Background: There are no known predictive markers for the efficacy of vascular endothelial growth factor (VEGF) pathway-targeted therapies. HTN and PTN are known side effects of anti-VEGF therapy. The aim of our study was to assess if HTN and/or PTN with bevacizumab (Bev) or VEGF receptor tyrosine kinase inhibitors (TKI) are associated with clinical outcomes in patients (pts) with mCRC. Methods: We conducted a retrospective analysis of pts with histologically proven mCRC treated with either Bev or TKI in combination with chemotherapy at The Christie Hospital from 2006 to 2009. Results: Of 90 pts evaluated, 50 were eligible. 17 (34%), 4 (8%), and 3 (6%) pts developed Common Toxicity Criteria (CTC) (v 3.0) Grade (Gr) 1, Gr 2 and Gr 3 HTN, respectively. None developed ≥ Gr 4 HTN. Median time to onset of ≥ Gr 2 HTN was 9 (range 2-22) weeks. Response rates (RR) were 42% for pts with Gr 0-1 HTN compared to 86% for pts with ≥ Gr 2 HTN (p=0.043). Median progression free survival (PFS) was 9.4 months for pts with Gr 0-1 HTN and 10.9 months for pts with ≥ Gr 2 HTN (p=0.336). Median overall survival (OS) was 21.6 months for pts with Gr 0-1 HTN and 25.2 months for pts with ≥ Gr 2 HTN (p=0.270). 12 pts (24%) developed Gr 1 PTN and 4 pts (8%) developed ≥ Gr 2 PTN. Median time to onset of ≥ Gr 2 PTN was 12 (range 4-29) weeks. Median OS was 23.9 months for pts with Gr 0-1 PTN and 4.2 months for those with ≥ Gr 2 PTN (p=0.028). No pt with ≥ Gr 2 PTN had pre-existing renal disease. 2/4 pts with ≥ Gr 2 PTN had HTN which was controlled prior to starting antiangiogenic therapy. There was no significant correlation between the development of PTN with either PFS or RR. No significant association was found between the development of HTN and PTN on therapy. Conclusions: To our knowledge, this is the first study demonstrating the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for mCRC. Whilst HTN is predictive of a significantly higher RR, the development of PTN during treatment with Bev or TKI portends poorer survival and should be evaluated prospectively. Gr 0-1 HTN ≥ Gr 2 HTN P value Gr 0-1 PTN ≥ Gr 2 PTN P value RR (%) 42 86 0.043 45 75 0.271 PFS (m) 9.4 10.9 0.336 9.4 4.1 0.362 OS (m) 21.6 25.2 0.270 23.9 4.2 0.028 No significant financial relationships to disclose.