A new retrospective exploratory analysis has found no association between treatment with sorafenib and the development of sarcopenia among patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer. However, this analysis, which was published recently in Thyroid, did find that sorafenib had a significant effect on muscle mass.
1However, this analysis, which was published recently inThyroid, did find that sorafenib had a significant effect on muscle mass.
The authors, led by Olivier Huillard, MD, PhD, Cochin Hospital, AP-HP, Paris, determined that approximately half of the patients receiving sorafenib were at risk of sarcopenia at baseline (n = 89/180; 49.4%). After 6 months, the mean weight, body mass index, and lean body mass of patients who received sorafenib were lower than at baseline. They were also significantly lower than for patients who received placebo (allP<0.0001).
The authors defined sarcopenia in men as the skeletal muscle (SM) index less than the median SM index value for men in the sarcopenia analysis set (SAS). For female patients, it was defined as the SM index less than the median SM index value for women in the SAS.
“Sorafenib significantly improves progression-free survival compared with placebo in patients with progressive radioactive iodine-refractory DTC, but its effects on muscle mass, and the associated adverse effects on prognosis, may partially negate these benefits,” Huillard et al wrote. “Consequently, every effort should be made to prevent muscle wasting through nutritional support and appropriate exercise programs. Conversely, other targeted agents may be associated with gain in muscle mass over time.”
This study was based on data from the phase III DECISION trial (NCT00984282), which was the basis of FDA approval of sorafenib for DTC.2Patients from that trial were eligible to be included in this new analysis if their baseline data included a computed tomography scan that allowed the authors to determine each patient’s muscle mass and SM index at the time of treatment initiation. The study’s end points were changes in body composition, dose modification (DMT), DMT within 1 month, severe toxic events (STEs), and early STEs.
The authors found that 365 of 419 patients in the DECISION trial were eligible for this analysis, 180 from the sorafenib group and 185 from the placebo group. Baseline characteristics were well-balanced between groups and, as expected, female patients had lower mean weight, SM area, SM index, and lean body mass than did men.
Huillard et al found wide geographic distribution among patients who had sarcopenia at baseline. Nearly half of European patients had sarcopenia (n = 46/104, 44.2%), while only about one-third of North American patients did (n = 10/31, 32.3%). In contrast, nearly three-fourths of Asian patients had sarcopenia at baseline (n = 33/45, 73.3%). They also found that patients who had baseline sarcopenia tended to be older and have lower body weight and SM characteristics.
Among patients who received sorafenib, their mean body weight, BMI and lean body mass had all decreased at 6 months compared to baseline. Their mean weight decreased by 5.0 kg (standard deviation [SD] 3.9). The mean BMI decreased by 1.8 kg/m2 (SD 1.4), and the mean lean body mass decreased by 3.0 kg (SD 2.5). In contrast, placebo-group patients saw either no change in these variables or a mean decrease of only 0.1 kg.
Approximately half of the sorfenib patients received a DMT during treatment (n = 102, 56.7%). In patients with sarcopenia, the median time to DMT was 58 days (95% Confidence Interval [CI], 13-148 days), but for nonsarcopenic patients, that interval was a median of 140 days (95% CI, 34-NA).
Sarcopenic patients who received sorafenib had a median time to STE of 147 days (95% CI, 58-NA). Sorafenib patients without sarcopenia did not reach their median time to STE. Huillard et al noted a nonsignificant trend toward a shorter time to DMTs and STEs in sarcopenic patients compared with nonsarcopenic patients (DMT analysis,P=0.178; STE analysis,P=0.172).
“Patients with sarcopenia receiving sorafenib have an important risk of toxicity that is not significantly different from that of patients without sarcopenia; no associations were found between sarcopenia and DMT or early DMT in these patients with DTC,” Huillard et al wrote. “This contrasts with observations in patients with hepatocellular carcinoma and renal cell carcinoma, which showed that sarcopenia was associated with toxicity, which might be attributed to differences in underlying disease and prior treatment.”
Study limitations include its exploratory nature, meaning that this analysis was not prespecified in the original protocol. Additionally, usable CT scans were not available for every patient in the DECISION trial, introducing the possibility of selection bias. Applying the same definition of sarcopenia across all ethnic groups is another limitation, as is the fact that the chosen sarcopenia definition has not been formally validated.