Lee Su Jin, Kim Tae Min, 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
Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Oncologist. 2015 Nov;20(11):1312-9. doi: 10.1634/theoncologist.2015-0161. Epub 2015 Sep 30.
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.
We conducted a 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.
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 KIT mutations, KIT amplifications, and both KIT mutations 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%-28.0%) and a disease control rate of 57.1% (95% CI: 42.1%-72.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KIT mutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only.
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.
KIT aberration can be detected in a subset of metastatic melanoma patients. This phase II trial showed that nilotinib demonstrates durable response in a subset of patients with KIT mutations. The safety profile was very tolerable. This study suggests that a KIT inhibitor may benefit a small subset of metastatic melanoma patients with KIT mutations.
已有研究表明，KIT可能是恶性黑色素瘤的一个潜在治疗靶点。我们评估了KIT抑制剂尼洛替尼对携带KIT基因突变或扩增的转移性黑色素瘤患者的抗肿瘤活性和安全性。
我们开展了一项尼洛替尼用于治疗伴有KIT突变或扩增的转移性恶性黑色素瘤的II期多中心试验。患者每日口服尼洛替尼400mg，分两次服用。主要终点为缓解率，如果在累计的36例患者中观察到7例或更多缓解者，则认为尼洛替尼值得在该研究人群中进一步测试。
2009年10月至2013年6月期间，176例患者接受了KIT基因异常的分子筛查，42例携带KIT基因突变和/或扩增的患者入组本研究。总体而言，分别有25例（59.5%）、15例（35.7%）和2例（4.8%）患者存在KIT突变、KIT扩增以及KIT突变与扩增并存的情况。在42例入组患者中，1例患者达到完全缓解，6例患者达到部分缓解，17例患者疾病稳定，总缓解率为16.7%（95%置信区间[CI]：5.4%-28.0%），疾病控制率为57.（95%CI：42.1%-72.1%）。缓解的中位持续时间为34周（范围：5-55周）。在7例缓解者中，6例患者存在KIT突变（外显子11：5例患者；外显子17：1例患者），1例患者仅存在KIT扩增。
尽管本研究未达到其主要终点缓解率，但尼洛替尼在一部分具有特定KIT突变的转移性黑色素瘤患者中显示出持久的缓解效果。
在一部分转移性黑色素瘤患者中可检测到KIT异常。这项II期试验表明，尼洛替尼在一部分具有KIT突变的患者中显示出持久的缓解效果。安全性非常好，耐受性良好。本研究提示，KIT抑制剂可能使一小部分具有KIT突变的转移性黑色素瘤患者获益。
