Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification

Jun Guo, Lu Si, Yan Kong, Keith T. Flaherty, Xiaowei Xu, Yanyan Zhu, Christopher Corless, Li Li, Haifu Li, Xinan Sheng, Chuanliang Cui, Zhihong Chi, Siming Li, Mei Han, Lili Mao, Xuede Lin, Nan Du, Xiaoshi Zhang, Junling Li, Baocheng WangShukui Qin

Research output: Contribution to journalArticle

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Abstract

Purpose: Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications. Patients and Methods: Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d. Results: Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P <.001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD. Conclusion: Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.

Original languageEnglish (US)
Pages (from-to)2904-2909
Number of pages6
JournalJournal of Clinical Oncology
Volume29
Issue number21
DOIs
StatePublished - Jul 20 2011

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Melanoma
Mutation
Disease-Free Survival
Disease Progression
Imatinib Mesylate
Survival Rate
Protein-Tyrosine Kinases
Exons
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. / Guo, Jun; Si, Lu; Kong, Yan; Flaherty, Keith T.; Xu, Xiaowei; Zhu, Yanyan; Corless, Christopher; Li, Li; Li, Haifu; Sheng, Xinan; Cui, Chuanliang; Chi, Zhihong; Li, Siming; Han, Mei; Mao, Lili; Lin, Xuede; Du, Nan; Zhang, Xiaoshi; Li, Junling; Wang, Baocheng; Qin, Shukui.

In: Journal of Clinical Oncology, Vol. 29, No. 21, 20.07.2011, p. 2904-2909.

Research output: Contribution to journalArticle

Guo, J, Si, L, Kong, Y, Flaherty, KT, Xu, X, Zhu, Y, Corless, C, Li, L, Li, H, Sheng, X, Cui, C, Chi, Z, Li, S, Han, M, Mao, L, Lin, X, Du, N, Zhang, X, Li, J, Wang, B & Qin, S 2011, 'Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification', Journal of Clinical Oncology, vol. 29, no. 21, pp. 2904-2909. https://doi.org/10.1200/JCO.2010.33.9275
Guo, Jun ; Si, Lu ; Kong, Yan ; Flaherty, Keith T. ; Xu, Xiaowei ; Zhu, Yanyan ; Corless, Christopher ; Li, Li ; Li, Haifu ; Sheng, Xinan ; Cui, Chuanliang ; Chi, Zhihong ; Li, Siming ; Han, Mei ; Mao, Lili ; Lin, Xuede ; Du, Nan ; Zhang, Xiaoshi ; Li, Junling ; Wang, Baocheng ; Qin, Shukui. / Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 21. pp. 2904-2909.
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abstract = "Purpose: Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications. Patients and Methods: Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d. Results: Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6{\%}. Rate of total disease control was 53.5{\%}: 10 patients (23.3{\%}; 95{\%} CI, 10.2{\%} to 36.4{\%}) and 13 patients (30.2{\%}; 95{\%} CI, 16.0{\%} to 44.4{\%}) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9{\%}) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0{\%}. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P <.001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD. Conclusion: Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3{\%}. Escalation to 800 mg/d could not restore disease control.",
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T1 - Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification

AU - Guo, Jun

AU - Si, Lu

AU - Kong, Yan

AU - Flaherty, Keith T.

AU - Xu, Xiaowei

AU - Zhu, Yanyan

AU - Corless, Christopher

AU - Li, Li

AU - Li, Haifu

AU - Sheng, Xinan

AU - Cui, Chuanliang

AU - Chi, Zhihong

AU - Li, Siming

AU - Han, Mei

AU - Mao, Lili

AU - Lin, Xuede

AU - Du, Nan

AU - Zhang, Xiaoshi

AU - Li, Junling

AU - Wang, Baocheng

AU - Qin, Shukui

PY - 2011/7/20

Y1 - 2011/7/20

N2 - Purpose: Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications. Patients and Methods: Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d. Results: Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P <.001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD. Conclusion: Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.

AB - Purpose: Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications. Patients and Methods: Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d. Results: Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P <.001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD. Conclusion: Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.

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