Body composition as a predictor of sunitinib toxicity in patients with renal cell carcinoma.
e15566 Background: Sunitinib is a standard first-line option for metastatic renal cell cancer (mRCC). Identification of biomarkers associated with outcome or toxicity is a challenge. Body composition is a prognostic factor in cancer and sarcopenia is associated with treatment toxicity and survival. We investigated if body composition by CT scan predicted dose limiting toxicity (DLT) from sunitinib in mRCC. Methods: Patients (pts) with mRCC receiving sunitinib 50mg as 1stline therapy between 2007-2012 were included. Ethical approval was obtained and prospectively maintained databases analysed. Skeletal muscle cross-sectional area at L3 was measured by CT. Sarcopenia was defined using published cut offs. Toxicity was assessed after 4 cycles of drug (CTCAE, v4.0). Results: 55 pts (43 male), mean age 64yrs (±10.6) were included. 67% were overweight/obese (BMI>25kg/m2). Sarcopenia was present in 33% (56% of normal BMI, 44% overweight group). Overall 40 pts (73%) experienced DLT (51% M, 100% F, p<0.016). DLT occurred in <6 months in 53% (44% M vs 83% F, p<0.016) and these pts were older (mean 68 yrs vs 60 yrs, p<0.01), had lower skeletal muscle mass (51.8 cm2/m2 vs 59.4 cm2/m2, p<0.012), and fat free mass (FFM) (51.4kg vs 57.7kg, p<0.03), and received higher drug dose in mg/kg FFM (1.01 vs 0.89, p<0.02). Common toxicities were GI (65%) and fatigue (47%). Of pts <25th percentile skeletal muscle mass 92% experienced DLT, higher than pts >75th percentile (p<0.05). Pts <25th percentile had an average of 5 toxicities vs 2 in those >75th percentile (p<0.003). All toxicities were more common in muscle wasted patients (p<0.05). 77% (n=10) of pts receiving a drug dose >75th percentile (1.105mg/FFM) experienced DLT in <6 months vs 44% (n=17) receiving a dose <75thpercentile (<1.099mg/FFM; p<0.037). Conclusions: Sarcopenia is prevalent in patients with mRCC, is easily measured, is an occult condition in pts with normal/high BMI, and is a significant predictor of DLT in pts receiving 1st line sunitinib. Our results highlight the potential use of baseline body composition to predict toxicity. The role of sarcopenia in targeted therapy is evolving and its potential to predict toxicity should be further studied.