Metabolic response by FDG-PET correlates with exon11 KIT mutation in patients with mucosal or acral melanoma or melanoma arising on chronically sun damaged skin treated with imatinib in a phase II trial

Objectives We hypothesize that metabolic response to imatinib (IM) by FDG-PET correlates with exon11 KIT mutation in patients (pts) with mucosal or acral melanoma or melanoma arising on chronically sun damaged skin and may predict outcome.

Methods 18 pts with these types of melanoma were treated with IM (400 mg po daily) in a phase II trial and had evaluable FDG-PET prior to and after 4 weeks of therapy. SUVmax was measured in up to 10 lesions per pt. Metabolic response (MPR, MSD, or MPD) was assessed using EORTC criteria based on thresholds for % SUVmax change relative to baseline (MPR ≤ -25% < MSD < +25% ≤ MPD). RECIST criteria were applied to diagnostic CT or MRI obtained after 6 wks of therapy and then at 2 month intervals. KIT mutation was determined by tumor biopsy in all pts. FDG-PET analysis was performed without knowledge of the mutation analysis, RECIST, or outcome.

Results MPR was seen in 5/18 (28%), MSD in 5/18 (28%), and MPD in 8/18 (44%). Out of the 5/18 (28%) pts with exon11 KIT mutation, 4/5 (80%) had MPR and 1/5 (20%) had MPD. Out of 13/18 (72%) pts without exon11 KIT mutation, only 1/13 (8%) had MPR, 5/13 (38%) had MSD and 7/13 (54%) had MPD. There was agreement of FDG-PET response at 1 month and best response by RECIST in 13/18 (72%). In 4/18 (22%) there was MPR on both FDG-PET and RECIST and all of these pts had the exon11 KIT mutation. Although time to progression was <4 months in all pts, median overall survival was 12.9 months in pts with exon11 KIT mutation compared to 4.8 months with another mutation.

Conclusions These findings suggest that metabolic response by FDG-PET correlates with exon11 KIT mutation in pts with these types of melanoma treated with IM and may be a helpful predictor of outcome