SECOND LINE NILOTINIB FOR c-KIT MELANOMAS

Clin Cancer Res. 2015 Feb 18. pii: clincanres.1630.2014. [Epub ahead of print]

Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition.

Carvajal RD1, Lawrence DP2, Weber J3, Gajewski TF4, Gonzalez R5, Lutzky J6, O'Day SJ7, Hamid O8, Wolchok JD9, Chapman PB10, Sullivan RJ11, Teitcher JB12, Ramaiya NH13, Giobbie-Hurder A14, Antonescu CR15, Heinrich MC16, Bastian B17, Corless CL18, Fletcher JA19, Hodi FS20.

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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 is unknown. Experimental Design: We conducted a phase II study of nilotinib 400 mg BID 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 and overall survival. A Simon two-stage 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-Cohort A; 8-Cohort B). Three patients on Cohort A (27%; 95% 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 time-to-progression and overall survival 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. Conclusion: 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.