Relationship between sarcopenia and dose-limiting toxicity (DLT) of sorafenib (SOR) in patients (pts) with advanced radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC) in the phase III DECISION trial.

Abstract

e17594 Background: In the phase III DECISION trial comparing SOR with placebo, pts with advanced RAI-R DTC treated with SOR experienced higher rates of adverse events (AEs) than pts with renal cell carcinoma and hepatocellular carcinoma treated with SOR (Brose et al. Lancet 2014). We hypothesized that long-term thyroxine suppressive therapy might result in a high prevalence of sarcopenia, which is known to be associated with increased toxicity of SOR (Antoun et al. Ann Oncol 2010), and we investigated whether sarcopenia at baseline correlated with DLT. Methods: In DECISION, pts with an analyzable baseline lumbar CT scan were eligible. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured, and the median value for each sex defined the cut-off points for sarcopenia. DLT was defined as any AE leading to dose modification; early toxicities occurred ≤30 days after treatment initiation. Results: Of 365 eligible pts, 199 (55%) were sarcopenic (SOR n = 100, placebo n = 99) with large geographic differences: 65/91 Asians (71%), 29/62 North Americans (47%), and 105/212 Europeans (50%). Sarcopenia was 3-fold more frequent than non-sarcopenia in pts ≥75 years of age (19% vs 6%) and was associated with lower body weight (mean [standard deviation]: 71.3 [16.8] vs 80.8 [19.5]; P < 0.0001). Among SOR pts, 76/180 (42%) experienced early DLT of which 44/76 (58%) occurred in sarcopenic pts (P = 0.6497). Among the 90 males, 61 (68%) were sarcopenic and of the 35 males with early DLT, 27 (77%) were sarcopenic. Median time to DLT in sarcopenic vs non-sarcopenic pts who received SOR was 63 vs 95 days, respectively (log-rank P = 0.5328). Conclusions: In this exploratory analysis from DECISION, approximately half of the pts were sarcopenic. In the overall population, no association between sarcopenia and early DLT or DLT were found. Clinical trial information: NCT00984282.