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Other approved treatments were not evaluated within a first-line setting and exhibit severe adverse events that limit QoL. Nilotinib was evaluated within this setting in GIST with a safety profile comparable to imatinib and effectiveness within KIT-exon-11-mutant GIST subgroup (ENESTg1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials, patients, and methods<\/jats:title>\n                    <jats:p>This is a retrospective case series reporting the outcome and side effects of 20 patients treated with nilotinib following severe imatinib toxicity. Nilotinib efficacy was tested in GIST cell lines carrying common primary and resistance mutations in KIT. Inhibitory profile of nilotinib was characterized using in silico modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In our retrospective analysis of 1263 patients, 7.3% of patients discontinued imatinib due to toxicity. In 20 patients who received nilotinib, reasons were skin (n\u2009=\u200911) and liver (n\u2009=\u20094) toxicity, followed by cardiac (n\u2009=\u20092) and gastrointestinal toxicities (n\u2009=\u20092). No cross-toxicities were observed with nilotinib treatment. Nilotinib was effective after imatinib intolerance. A secondary KIT Exon 9 mutation was found in a progressing lesion. In vitro viability assays showed effectiveness in KIT-Exon-11-mutant cell lines, but not in Exon 9 or imatinib-resistant mutations in doses deemed clinically achievable. In silico modeling revealed steric hindrance by Exon 9 or imatinib resistance mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Nilotinib exhibits no cross toxicity with imatinib and represents an important alternative in imatinib-sensitive, KIT-exon-11-mutant GIST given its excellent toxicity profile. There is no biological rationale for the use of nilotinib in imatinib-resistant GIST with secondary KIT mutations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag345","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:31:16Z","timestamp":1788460276000},"source":"Crossref","is-referenced-by-count":0,"title":["Nilotinib revisited in GIST: salvage use in patients with severe imatinib toxicity"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-7121","authenticated-orcid":false,"given":"Johanna","family":"Falkenhorst","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Duisburg-Essen, Medical School , Essen, 45122,","place":["Germany"]},{"name":"DKTK Partner Site Essen, German Cancer Consortium (DKTK) , Heidelberg, 69120,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) West , Essen, 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