Posted: Wednesday, September 28, 2022
An in vivo imaging biomarker, 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT), may be a beneficial tool for predicting response to treatment with the CDK4/6 inhibitor palbociclib in patients with bladder cancer, revealed a preclinical study published in the Journal of Translational Medicine. According to James H. Doroshow, MD, of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland, and colleagues, significant decreases in [18F]FLT PET uptake were observed as early as 3 days after initiation of therapy with palbociclib—both alone and in combination with temozolomide. This study is reportedly the first of [18F]FLT and CDK4/6 inhibitors in solid tumor models outside of breast cancer.
In this exploratory study, 24 next-generation sequencing, mice-bearing, patient-derived xenografts of a bladder tumor were randomly assigned to one of four treatment groups: vehicle (n = 6); palbociclib (n = 6); temozolomide (n = 6); and palbociclib plus temozolomide (n = 6). Each mouse was treated with two cycles of therapy or vehicle.
At days 3 and 9, [18F]FLT uptake decreased significantly in the palbociclib and combination arms (P = .0423 and .0106, respectively, at day 3, and .0012 and 0.0031 at day 9) with stable tumor volume. Temozolomide as a single agent was not found to be effective, and early increased [18F]FLT uptake was observed; at day 9, uptake was significantly different from baseline (P = .0418), and progressive tumor growth was noted during the treatment phase. By day 22—a total of 10 days after cessation of the treatment phase—all groups demonstrated progressive tumor growth.
“These results support early modulation of [18F]FLT as an in vivo biomarker predictive of palbociclib therapy response in a non–breast cancer model,” concluded the authors.
Disclosure: The study authors reported no conflicts of interest.