Clinical and genomic correlates of imatinib response in melanomas with KIT alterations Journal Article
| Authors: | Jung, S.; Armstrong, E.; Wei, A. Z.; Ye, F.; Lee, A.; Carlino, M. S.; Sullivan, R. J.; Carvajal, R. D.; Shoushtari, A. N.; Johnson, D. B. |
| Article Title: | Clinical and genomic correlates of imatinib response in melanomas with KIT alterations |
| Abstract: | 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. © 2022, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | adult; clinical article; controlled study; human tissue; treatment response; aged; retrospective studies; unclassified drug; gene mutation; overall survival; exon; genetics; mutation; clinical feature; clinical trial; histopathology; advanced cancer; antineoplastic agents; united states; antineoplastic agent; prospective study; prospective studies; imatinib; stem cell factor receptor; proto-oncogene proteins c-kit; cancer immunotherapy; melanoma; progression free survival; clinical assessment; prevalence; cohort analysis; pathology; protein tyrosine kinase; retrospective study; multicenter study; clinical evaluation; data analysis; genomics; australia; multivariate analysis; hazard ratio; cancer of unknown primary site; cytotoxic t lymphocyte antigen 4; protein kit; b raf kinase; cutaneous melanoma; imatinib mesylate; phase 2 clinical trial (topic); clinical outcome; demographics; mucosal melanoma; overall response rate; acral melanoma; protein nras; humans; human; male; female; article; gilvetmab; stratified sample |
| Journal Title: | British Journal of Cancer |
| Volume: | 127 |
| Issue: | 9 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2022-11-01 |
| Start Page: | 1726 |
| End Page: | 1732 |
| Language: | English |
| DOI: | 10.1038/s41416-022-01942-z |
| PUBMED: | 35999272 |
| PROVIDER: | scopus |
| PMCID: | PMC9596433 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |
