Survival and Early FDG PET Response to BRAF and MEK Inhibition in Patients with BRAF-mutant Melanoma

Objectives Metabolic response to treatment measured by FDG PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on FDG PET-CT for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy.

Methods 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (GDC-0973 or trametinib), and were imaged at baseline and shortly thereafter with FDG PET-CT. Each scan yielded two values of 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 EORTC criteria. Associations between overall survival (OS), progression-free survival (PFS) and changes in SUVmax were examined.

Results Mean time to follow-up FDG PET-CT was 26 days. At follow-up, 2 patients had a complete response. For the most metabolically active focus, 22 patients had a partial response. For the least responsive focus, 18 patients had a partial response, 2 had stable disease and 2 had progressive disease. For the most metabolically active tumor, no association was observed between change in SUVmax and OS (p=0.73) or PFS (p=0.17). For the least responsive tumor, change in SUVmax was associated with PFS (HR=1.34, 95% CI: 1.06 to 1.71, p=0.01), but not OS (p=0.52). ECOG score was associated with OS (HR=11.81, 95% CI: 1.42 to 97.60, p=0.02) and PFS (HR=24.72, 95% CI: 3.23 to 189.42, p=0.002).

Conclusions Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for progression-free survival in patients with BRAF-mutant melanoma.