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

Purpose Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on ¹⁸F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy. Materials and methods 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 ¹⁸F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUV_max): 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 SUV_max. Results The mean time to follow-up ¹⁸F-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 SUV_max and OS (P=0.73) or PFS (P =0.17). For the least responsive tumor, change in SUV_max 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). Conclusion Change in SUV_max for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.