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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Nilotinib in patients with metastatic melanoma harboring KIT gene aberration
Jin Hyun Cho1, Kyoung Mee Kim, Miyeon Kwon
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.
Purpose:
Patients with metastatic melanoma have a poor prognosis and few treatment options are available. We evaluated the anti-tumor activity and safety of nilotinib, a KIT inhibitor, in patients with metastatic melanoma harboring KIT alterations, either mutations or amplifications.
Patients And Methods:
This study was open-label, single center, prospective phase II clinical trial. Between October 2009 and April 2011, 11 patients with metastatic melanoma harboring KIT gene mutations or KIT gene amplifications were enrolled in the first stage of phase II study and nilotinib was administered orally at a dose of 400 mg twice a day until disease progression or intolerable toxicities. The primary endpoint was response rate and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).
Results:
Of 11 patients, 9 patients were evaluable for treatment response. Of 9 patients, three patients had KIT mutations in exon 11, Leu576Pro, Val559Ala and Lys558Arg; and 6 patients had KIT amplifications > 50 copies compared to control DNA. Two patients achieved partial response (22.2%) and 5 patients achieved stable disease (55.6%). In two patients who responded to nilotinib, both had KIT mutations and showed durable response for 8.4 months and 10.0+ months. Of note, one patient with KIT amplification had stable disease with response for 6 months. A decrease in tumor size from baseline was observed in four patients (44.4%). Nilotinib 800 mg/d was very well tolerated with grade 1 nausea and grade 1 dry-eye being the most common adverse events.
Conclusions:
We have decided to publish the preliminary results because anti-tumor activity of nilotinib was promising in KIT mutated patients. Although our results are preliminary, nilotinib had very favorable toxicity profile with durable response in metastatic melanoma patients with KIT mutations. The anti-tumor activity of nilotinib in melanoma patients with KIT amplification is yet to be determined in future studies. Currently, phase II nilotinib trial is ongoing in Korea as multi-center study.
Insights
Nilotinib shows promising anti-tumor activity and a favorable safety profile in metastatic melanoma patients with KIT mutations. Further studies are needed to determine its efficacy in patients with KIT amplification.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Metastatic melanoma presents a poor prognosis with limited therapeutic options.
- KIT alterations (mutations or amplifications) are found in some melanoma cases.
- Targeted therapies are being investigated for melanoma with specific genetic profiles.
Purpose of the Study:
- To evaluate the anti-tumor activity and safety of nilotinib, a KIT inhibitor.
- To assess nilotinib's efficacy in patients with metastatic melanoma harboring KIT alterations.
- To determine response rate, progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Open-label, single-center, prospective phase II clinical trial.
- 11 patients with metastatic melanoma and KIT mutations or amplifications were enrolled.
- Nilotinib (400 mg twice daily) was administered until disease progression or toxicity.
Main Results:
- Among 9 evaluable patients, 2 (22.2%) had partial response and 5 (55.6%) had stable disease.
- Durable responses were observed in patients with KIT mutations (8.4 and 10.0+ months).
- Nilotinib was well-tolerated, with nausea and dry eye as the most common adverse events.
Conclusions:
- Preliminary results indicate promising anti-tumor activity and a favorable toxicity profile for nilotinib in KIT-mutated melanoma.
- Nilotinib demonstrated durable responses in patients with KIT mutations.
- Further investigation is required to establish nilotinib's efficacy in melanoma patients with KIT amplification.
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