Open AccessFDG ‐ PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer
Author(s) -
Chen James L.,
Appelbaum Daniel E.,
Kocherginsky Masha,
Cowey Charles L.,
Kimryn Rathmell Wendy,
McDermott David F.,
Stadler Walter M.
Publication year - 2013
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.102
Subject(s) - everolimus , medicine , standardized uptake value , renal cell carcinoma , clinical endpoint , positron emission tomography , biomarker , response evaluation criteria in solid tumors , cancer , oncology , nuclear medicine , chemotherapy , progressive disease , clinical trial , biology , biochemistry
The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma ( RCC ) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG ‐ PET ([ 18 F] fluorodeoxy‐glucose positron emission tomography) may predict antitumor activity. Metastatic RCC ( mRCC ) patients refractory to vascular endothelial growth factor ( VEGF ) pathway inhibition were treated with standard dose everolimus. FDG ‐ PET scans were obtained at baseline and 2 weeks; serial computed tomography ( CT ) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2‐week relative changes were examined for association with 8‐week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre‐ and 2‐week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)‐based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression‐free survival ( PFS ) ( P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUV s on follow‐up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG ‐ PET ‐based biomarkers is challenged by high variability.