Regorafenib (REG) have been approved as salvage treatment for patients with metastatic colorectal cancer (mCRC). Tumor metabolic analysis using FDG-PET/CT has been reported to be more sensitive to predict the response of molecular targeting agents, as compared with the change of tumor burden using conventional CT. We conducted a prospective study to evaluate the efficacy of REG in mCRC patients by the assessment using FDG-PET/CT.
Patients with mCRC refractory to standard chemotherapies with measurable lesions according to RECIST (Ver. 1.1) criteria, which are also assessable by FDG-PET/CT, enrolled in this study. REG was given orally in a dose of 160 mg once-daily for 3 weeks, followed by 1 week of rest. After the first cycle, FDG-PET/CT was performed again to assess the chronological change in the SUV max as compared with that before the treatment. The primary endpoint is the chronological change in SUV max in the legion, of which value is highest in pretreatment FDG-PET/CT. Metabolic response and size-based response were assessed according to EORTC PET and RECIST criterion, respectively, by independent external review. We set the null and alternative hypotheses at 0% and 10%, respectively. Assuming a one-sided alpha level of 2.5% and a power of ≥90%, we estimated that 16 subjects are required and set the target sample size at 20 patients.
From November 2014 to March 2016, 17 of all enrolled 20 patients were evaluated for metabolic response. Six and 11 patients had SD and PD for the best overall response according to the RECIST criteria, thus the DCR was 30.0% (95% CI, 11.9-54.3). As for the primary endpoint, the response rate was 5.9% (95% CI, 0.1-28.7) in all evaluable patients including one PR, 4 SD (23.5%) and 12 PD (70.6%). Based on the chronological changes of the sum of SUV max in all targeted legions up to 5, there were 5 SD (29.4%) and 12 PD (70.6%). When response was categorized into PD and non-PD (PR or SD), the metabolic response after the first cycle could predict the size-based response with a sensitivity of 83% and specificity of 100%.
We confirmed the efficacy of REG in mCRC patients by the assessment of metabolic response using FDG-PET/CT.
Clinical trial identification
UMIN000015563, Nov 01 2014
Legal entity responsible for the study
All authors have declared no conflicts of interest.