Abstract：
BACKGROUND: We conducted an open-label, single-arm, multi-center phase II trial to evaluate the efficacy and safety of imatinib chemotherapy-refractory or metastatic solid tumor patients with c-KIT mutations and/or amplification.
METHODS: c-KIT mutations and amplification were detected using NGS. Imatinib (400 mg daily) was administered continuously in 28-day cycles until disease progression, unacceptable adverse events, or death by any cause. The primary endpoint was the objective response rate (ORR).
RESULTS: In total, 18 patients were enrolled on this trial. The most common tumor type was melanoma (n = 15, 83.3%), followed by ovarian cancer, breast cancer, and metastasis of unknown origin (MUO) (each n = 1, 5.5%). The total number of evaluable patients was 17, of which one patient had a complete response, six patients had partial response, and two patients had stable disease. The overall response rate (ORR) of 41.2% (95% CI 17.80-64.60) and a disease control rate of 52.9% (95% CI 29.17-76.63). The median progression-free survival was 2.2 months (95% CI 1.29-3.20), and median overall survival was 9.1 months (95% CI 2.10-16.11). The most common adverse events were edema (31.3%), anorexia (25.0%), nausea (18.8%), and skin rash (18.8%).
CONCLUSIONS: Imatinib demonstrated modest anti-tumor activity and a manageable safety profile in chemotherapy-refractory solid tumors with c-KIT mutation, especially in melanoma patients.
METHODS: c-KIT mutations and amplification were detected using NGS. Imatinib (400 mg daily) was administered continuously in 28-day cycles until disease progression, unacceptable adverse events, or death by any cause. The primary endpoint was the objective response rate (ORR).
RESULTS: In total, 18 patients were enrolled on this trial. The most common tumor type was melanoma (n = 15, 83.3%), followed by ovarian cancer, breast cancer, and metastasis of unknown origin (MUO) (each n = 1, 5.5%). The total number of evaluable patients was 17, of which one patient had a complete response, six patients had partial response, and two patients had stable disease. The overall response rate (ORR) of 41.2% (95% CI 17.80-64.60) and a disease control rate of 52.9% (95% CI 29.17-76.63). The median progression-free survival was 2.2 months (95% CI 1.29-3.20), and median overall survival was 9.1 months (95% CI 2.10-16.11). The most common adverse events were edema (31.3%), anorexia (25.0%), nausea (18.8%), and skin rash (18.8%).
CONCLUSIONS: Imatinib demonstrated modest anti-tumor activity and a manageable safety profile in chemotherapy-refractory solid tumors with c-KIT mutation, especially in melanoma patients.
摘要：
背景：我们进行了开放标签，单臂,多中心II期试验,以评估具有c-KIT突变和/或扩增的伊马替尼化疗难治性或转移性实体瘤患者的疗效和安全性.
方法：使用NGS检测c-KIT突变和扩增。伊马替尼（每天400毫克）在28天的周期内连续给药，直到疾病进展，不可接受的不良事件，或因任何原因死亡。主要终点是客观缓解率(ORR)。
结果：总计，该试验招募了18名患者。最常见的肿瘤类型是黑色素瘤（n=15，83.3%），其次是卵巢癌，乳腺癌,和未知来源的转移（MUO）（每个n=1，5.5％）。可评估的患者总数为17，其中一名患者完全缓解，六名患者有部分反应，两名患者病情稳定。总有效率（ORR）为41.2%（95%CI17.80-64.60），疾病控制率为52.9%（95%CI29.17-76.63）。中位无进展生存期为2.2个月(95%CI1.29-3.20),中位总生存期为9.1个月(95%CI2.10-16.11).最常见的不良事件是水肿（31.3%），厌食症（25.0%），恶心（18.8%），皮疹(18.8%)。
结论：伊马替尼在具有c-KIT突变的化疗难治性实体瘤中表现出适度的抗肿瘤活性和可控的安全性，尤其是黑色素瘤患者。
方法：使用NGS检测c-KIT突变和扩增。伊马替尼（每天400毫克）在28天的周期内连续给药，直到疾病进展，不可接受的不良事件，或因任何原因死亡。主要终点是客观缓解率(ORR)。
结果：总计，该试验招募了18名患者。最常见的肿瘤类型是黑色素瘤（n=15，83.3%），其次是卵巢癌，乳腺癌,和未知来源的转移（MUO）（每个n=1，5.5％）。可评估的患者总数为17，其中一名患者完全缓解，六名患者有部分反应，两名患者病情稳定。总有效率（ORR）为41.2%（95%CI17.80-64.60），疾病控制率为52.9%（95%CI29.17-76.63）。中位无进展生存期为2.2个月(95%CI1.29-3.20),中位总生存期为9.1个月(95%CI2.10-16.11).最常见的不良事件是水肿（31.3%），厌食症（25.0%），恶心（18.8%），皮疹(18.8%)。
结论：伊马替尼在具有c-KIT突变的化疗难治性实体瘤中表现出适度的抗肿瘤活性和可控的安全性，尤其是黑色素瘤患者。
