Phase II study of nilotinib in melanoma harboring KIT alterations following progression to prior KIT inhibition Journal Article


Authors: Carvajal, R. D.; Lawrence, D. P.; Weber, J. S.; Gajewski, T. F.; Gonzalez, R.; Lutzky, J.; O'Day, S. J.; Hamid, O.; Wolchok, J. D.; Chapman, P. B.; Sullivan, R. J.; Teitcher, J. B.; Ramaiya, N.; Giobbie-Hurder, A.; Antonescu, C. R.; Heinrich, M. C.; Bastian, B. C.; Corless, C. L.; Fletcher, J. A.; Hodi, F. S.
Article Title: Phase II study of nilotinib in melanoma harboring KIT alterations following progression to prior KIT inhibition
Abstract: Purpose: Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown. Experimental Design: We conducted a phase II study of nilotinib 400 mg twice a day in two cohorts of patients with melanomas harboring KIT mutations or amplification: (A) those refractory or intolerant to a prior KIT inhibitor; and (B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression (TTP), and overall survival (OS). A Simon twostage and a single-stage design was planned to assess for the primary endpoint in cohorts A and B, respectively. Results: Twenty patients were enrolled and 19 treated (11 in cohort A; 8 in cohort B). Three patients on cohort A [27%; 95% confidence interval (CI), 8%-56%] and 1 on cohort B (12.5%; 90% CI, 0.6%-47%) achieved the primary endpoint. Two partial responses were observed in cohort A (18.2%; 90% CI, 3%-47%); none were observed in cohort B. The median TTP and OS was 3.3 (90% CI, 2.1-3.9 months) and 9.1 months (90% CI, 4.3-14.2 months), respectively, in all treated patients. Conclusions: Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT-altered melanoma with brain metastasis is limited. © 2015 AACR.
Keywords: adult; clinical article; human tissue; aged; gene mutation; overall survival; fatigue; drug dose reduction; unspecified side effect; imatinib; progression free survival; phase 2 clinical trial; gene amplification; gastrointestinal symptom; rash; hyponatremia; multicenter study; drug response; brain metastasis; pancreas enzyme; nilotinib; musculoskeletal disease; oncogene c kit; metastatic melanoma; hypertransaminasemia; very elderly; human; male; female; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 21
Issue: 10
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2015-05-15
Start Page: 2289
End Page: 2296
Language: English
DOI: 10.1158/1078-0432.ccr-14-1630
PROVIDER: scopus
PUBMED: 25695690
PMCID: PMC5013827
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    656 Wolchok
  2. Richard D Carvajal
    133 Carvajal
  3. Cristina R Antonescu
    606 Antonescu
  4. Paul Chapman
    246 Chapman