Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Department of Medical Oncology, Sarcoma Center/West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
ESMO Open. 2022 Aug;7(4):100520. doi: 10.1016/j.esmoop.2022.100520. Epub 2022 Jun 23.
Ripretinib, a broad-spectrum KIT and platelet-derived growth factor receptor A switch-control tyrosine kinase inhibitor, is approved for the treatment of adult patients with advanced gastrointestinal stromal tumor as ≥ fourth-line therapy. We present the efficacy and safety of ripretinib in patients with KIT-altered metastatic melanoma enrolled in the expansion phase of the ripretinib phase I study.
Patients with KIT-altered metastatic melanoma were enrolled and treated with ripretinib at the recommended phase II dose of 150 mg once daily in 28-day cycles. Investigator-assessed responses according to Response Evaluation Criteria In Solid Tumors version 1.1 were carried out on day 1 of cycles 3, 5, 7, every three cycles thereafter, and at a final study visit.
A total of 26 patients with KIT-altered metastatic melanoma (25 with KIT mutations, 1 with KIT-amplification) were enrolled. Patients had received prior immunotherapy (n = 23, 88%) and KIT inhibitor therapy (n = 9, 35%). Confirmed objective response rate (ORR) was 23% [95% confidence interval (CI) 9%-44%; one complete and five partial responses] with a median duration of response of 9.1 months (range, 6.9-31.3 months). Median progression-free survival (mPFS) was 7.3 months (95% CI 1.9-13.6 months). Patients without prior KIT inhibitor therapy had a higher ORR and longer mPFS (n = 17, ORR 29%, mPFS 10.2 months) than those who had received prior KIT inhibitor treatment (n = 9, ORR 11%, mPFS 2.9 months). The most common treatment-related treatment-emergent adverse events (TEAEs) of any grade in ≥15% of patients were increased lipase, alopecia, actinic keratosis, myalgia, arthralgia, decreased appetite, fatigue, hyperkeratosis, nausea, and palmar-plantar erythrodysesthesia syndrome. There were no grade ≥4 treatment-related TEAEs.
In this phase I study, ripretinib demonstrated encouraging efficacy and a well-tolerated safety profile in patients with KIT-altered metastatic melanoma, suggesting ripretinib may have a clinically meaningful role in treating these patients.
Ripretinib 是一种广谱 KIT 和血小板衍生生长因子受体 A 开关控制酪氨酸激酶抑制剂，被批准用于治疗成人晚期胃肠间质瘤患者，作为第四线治疗药物。我们报告了在 Ripretinib Ⅰ期研究扩展阶段入组的 KIT 改变转移性黑色素瘤患者中，ripretinib 的疗效和安全性。
入组 KIT 改变的转移性黑色素瘤患者，按照推荐的Ⅱ期剂量 150mg 每日一次，28 天为一周期，接受 Ripretinib 治疗。根据实体瘤反应评价标准 1.1 进行研究者评估的反应，在第 3、5、7 周期的第 1 天进行，此后每 3 个周期进行一次，以及最后一次研究访视时进行。
共有 26 例 KIT 改变的转移性黑色素瘤患者（25 例有 KIT 突变，1 例有 KIT 扩增）入组。患者既往接受过免疫治疗（n=23，88%）和 KIT 抑制剂治疗（n=9，35%）。确认的客观缓解率（ORR）为 23%（95%可信区间[CI]9%-44%；1 例完全缓解，5 例部分缓解），缓解持续时间的中位数为 9.1 个月（范围：6.9-31.3 个月）。中位无进展生存期（mPFS）为 7.3 个月（95%CI 1.9-13.6 个月）。未接受过 KIT 抑制剂治疗的患者的 ORR 和 mPFS 更高（n=17，ORR 29%，mPFS 10.2 个月），而接受过 KIT 抑制剂治疗的患者的 ORR 和 mPFS 较低（n=9，ORR 11%，mPFS 2.9 个月）。任何级别发生率≥15%的最常见的治疗相关不良事件（TEAEs）是脂肪酶升高、脱发、光化性角化病、肌痛、关节痛、食欲下降、疲劳、角化过度、恶心和掌跖红斑感觉不良综合征。没有发生≥4 级的治疗相关 TEAEs。
在这项Ⅰ期研究中，ripretinib 在 KIT 改变的转移性黑色素瘤患者中表现出令人鼓舞的疗效和良好的耐受性安全性，提示 ripretinib 在治疗这些患者方面可能具有临床意义。
