Evaluation of parameters for treatment duration of sunitinib in metastatic renal cell carcinoma.

Abstract

e15042 Background: In metastatic renal cell carcinoma (mRCC), there is a need for predictive indicators for treatment duration (TD) of sunitinib. Our study evaluates parameters that may be associated with TD of sunitinib. Methods: From 01/2007-12/2011, consecutive mRCC patients (pts) were reviewed. Responders (R) were defined as having either complete response (CR) or partial response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, while non-responders (NR) were defined as having either stable disease (SD) or progressive disease (PD). Long term duration (LTD) was defined as therapy with sunitinib ≥ 18 months (mos). Hazard ratios (HR) and 95% confidence interval (95CI) representing the association between TD and specific parameters were computed with Cox proportional hazard model. Results: After a median follow-up of 9.8 mos (<1 - 63.8) of 128 mRCC pts, 57 (45%) received sunitinib. Responses were CR, PR, SD, PD of 3, 13, 8 and 33 pts, respectively. LTD was observed in 9 pts (21%). Hemoglobin < 12.5 g/dL (p = 0.048), prior nephrectomy (PN) (p = 0.001), prior therapies (p = 0.016), dose reduction (DR) (p = 0.001), an increased skin toxicity (p = 0.025) and low/intermediate (LI) Memorial Sloan-Kettering Cancer Center (MSKCC) risk-groups (p = 0.003) were associated with longer TD and a higher ANC (p < 0.0001) with shorter TD. In the multivariate analysis, PN was the only significant prognostic factor [HR 0.3 (95CI 0.12 -0.72) p = 0.007] that was associated with prolonged TD. Pts with LTD had a lower baseline ANC (p= 0.037), a LI MSKCC (p = 0.026), higher frequency of DR (p = 0.007), increased skin (p = 0.017) and endocrine (p = 0.015) toxicities and an increase of body mass index (BMI) from baseline (p = 0.008). When adjusted for BMI and performance status, results were maintained. Progression free survival (PFS) and overall survival (OS) of pts with LTD were not reached. However, both PFS and OS of R with TD < 18 mos, were 19.5 mos 95CI (3.4 - 27.9). Conclusions: PN, lower baseline ANC, DR, an increase of BMI from baseline, skin and endocrine toxicities were associated with prolonged TD of sunitinib in mRCC. There is a need for prospective studies to develop a predictive TD model in this setting.