Treatment-related deterioration of renal function as a biomarker to predict antitumor efficacy of sunitinib in patients with metastatic renal cell carcinoma.

Abstract

502 Background: Some on-target adverse events such as hypertension or thrombocytopenia have been reported as biomarkers predicting the efficacy of sunitinib as first-line therapy for patients with metastatic renal cell carcinoma (mRCC). Decrease of renal function is a major adverse event of sunitinib. However, it remains unclear whether the degree of deterioration of renal function can predict the anti-tumor efficacy of sunitinib. We investigated the relationship between treatment-related deterioration of renal function and anti-tumor efficacy in mRCC patients treated with sunitinib. Methods: We retrospectively reviewed the medical records of mRCC patients who were treated with sunitinib for more than 3 months. Patients receiving hemodialysis before receiving sunitinib as well as those who did not undergo nephrectomy were excluded from our analysis. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the MDRD equation modified for Japanese patients. The degree of deterioration in eGFR was compared with progression-free survival (PFS). Results: Sixty-two patients were enrolled, the median age was 65 years, and 44 patients (71%) were male. The median baseline eGFR was 49.1 ml/min/1.73m2, and median decrease of eGFR was 9.9 ml/min/1.73m2. Forty-seven patients (76%) had a decreased eGFR of more than 10% compared to baseline values. The patients showing this decrease had significantly longer PFS than those who did not (PFS: 15.5 months vs. 6.1 months, respectively; p=0.001). On multivariate analysis, a decrease in eGFR of more than 10% was a significant independent factor for predicting longer PFS (hazard ratio, 0.37; 95% confidence interval, 0.17-0.83; p=0.017) as well as MSKCC risk groups and cycles of sunitinib. Conclusions: Treatment-related deterioration of renal function is a biomarker to predict better treatment efficacy for use of sunitinib during first-line therapy for patients with mRCC.