Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma.

Abstract

Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on (18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy. Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax. The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23-189.42, P=0.002). Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.