Phase II trial of nilotinib in patients with metastatic malignant melanoma harboring KIT gene aberration: A multicenter trial of Korean cancer study group (UN10-06)

Su Jin Lee, Taemin Kim, Yu Jung Kim, Kee Taek Jang, Hyo Jin Lee, Soon Nam Lee, Mi Sun Ahn, In Gyu Hwang, Suee Lee, Moon Hee Lee, Jeeyun Lee

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background. KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications. Methods.Weconducteda phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily.The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population. Results. Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2(4.8%)patients had KITmutations, KIT amplifications,andboth KITmutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%228.0%) and a disease control rate of 57.1% (95% CI: 42.1%272.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KITmutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only. Conclusion. Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.

Original languageEnglish
Pages (from-to)1312-1319
Number of pages8
JournalOncologist
Volume20
Issue number11
DOIs
StatePublished - 30 Sep 2015

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Multicenter Studies
Melanoma
Genes
Neoplasms
Mutation
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Exons
Confidence Intervals

Keywords

  • KIT amplification
  • KIT mutation
  • Melanoma
  • Nilotinib

Cite this

Lee, Su Jin ; Kim, Taemin ; Kim, Yu Jung ; Jang, Kee Taek ; Lee, Hyo Jin ; Lee, Soon Nam ; Ahn, Mi Sun ; Hwang, In Gyu ; Lee, Suee ; Lee, Moon Hee ; Lee, Jeeyun. / Phase II trial of nilotinib in patients with metastatic malignant melanoma harboring KIT gene aberration : A multicenter trial of Korean cancer study group (UN10-06). In: Oncologist. 2015 ; Vol. 20, No. 11. pp. 1312-1319.
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title = "Phase II trial of nilotinib in patients with metastatic malignant melanoma harboring KIT gene aberration: A multicenter trial of Korean cancer study group (UN10-06)",
abstract = "Background. KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications. Methods.Weconducteda phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily.The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population. Results. Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5{\%}), 15 (35.7{\%}), and 2(4.8{\%})patients had KITmutations, KIT amplifications,andboth KITmutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7{\%} (95{\%} confidence interval [CI]: 5.4{\%}228.0{\%}) and a disease control rate of 57.1{\%} (95{\%} CI: 42.1{\%}272.1{\%}). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KITmutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only. Conclusion. Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.",
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Phase II trial of nilotinib in patients with metastatic malignant melanoma harboring KIT gene aberration : A multicenter trial of Korean cancer study group (UN10-06). / Lee, Su Jin; Kim, Taemin; Kim, Yu Jung; Jang, Kee Taek; Lee, Hyo Jin; Lee, Soon Nam; Ahn, Mi Sun; Hwang, In Gyu; Lee, Suee; Lee, Moon Hee; Lee, Jeeyun.

In: Oncologist, Vol. 20, No. 11, 30.09.2015, p. 1312-1319.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of nilotinib in patients with metastatic malignant melanoma harboring KIT gene aberration

T2 - A multicenter trial of Korean cancer study group (UN10-06)

AU - Lee, Su Jin

AU - Kim, Taemin

AU - Kim, Yu Jung

AU - Jang, Kee Taek

AU - Lee, Hyo Jin

AU - Lee, Soon Nam

AU - Ahn, Mi Sun

AU - Hwang, In Gyu

AU - Lee, Suee

AU - Lee, Moon Hee

AU - Lee, Jeeyun

PY - 2015/9/30

Y1 - 2015/9/30

N2 - Background. KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications. Methods.Weconducteda phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily.The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population. Results. Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2(4.8%)patients had KITmutations, KIT amplifications,andboth KITmutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%228.0%) and a disease control rate of 57.1% (95% CI: 42.1%272.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KITmutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only. Conclusion. Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.

AB - Background. KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications. Methods.Weconducteda phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily.The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population. Results. Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2(4.8%)patients had KITmutations, KIT amplifications,andboth KITmutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%228.0%) and a disease control rate of 57.1% (95% CI: 42.1%272.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KITmutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only. Conclusion. Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.

KW - KIT amplification

KW - KIT mutation

KW - Melanoma

KW - Nilotinib

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DO - 10.1634/theoncologist.2015-0161

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