Clinical and Genomic Correlates of Imatinib Response in Melanomas with KIT Alterations.

Background Imatinib is an active agent for some patients with melanoma harbouring c-KIT alterations. However, the genetic and clinical features that correlate with imatinib sensitivity are not well-defined. Methods We retrospectively evaluated 38 KIT -altered melanoma patients from five medical centres who received imatinib, and pooled data from prospective studies of imatinib in 92 KIT -altered melanoma patients. Baseline patient and disease characteristics, and clinical outcomes were assessed. Results In the pooled analysis ( N = 130), alterations in exons 11/13 had the highest response rates (38% and 33%); L576P ( N = 23) and K642E ( N = 12) mutations had ORR of 52% and 42%, respectively. ORR was 38% (mucosal), 25% (acral), and 8% (unknown-primary). PFS appeared longer in exon 11/13 vs. exon 17 alterations (median 4.3 and 4.5 vs. 1.1 months; p = 0.19), with similar superiority in OS (median 19.7 and 15.4 vs. 12.1 months; p = 0.20). By histology, median PFS was 4.5 months (mucosal), 2.7 (acral), and 5.0 (unknown-primary) [ p = 0.36]. Median OS was 18.0 months (mucosal), 21.8 (acral), 11.5 (unknown-primary) [ p = 0.26]. In multivariate analyses, mucosal melanoma was associated with higher PFS and exon 17 mutations were associated with reduced PFS. Conclusion This multicenter study highlights KIT -alterations sensitive to imatinib and augments evidence for imatinib in subsets of KIT -altered melanoma.