Sotorasib对晚期实体瘤KRAS(G12C)的抑制作用
文章的细节
-
引用
复制到剪贴板 -
Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT
Sotorasib对晚期实体瘤KRAS(G12C)的抑制作用
中华外科杂志2020年9月24日;383(13):1207-1217。doi: 10.1056 / NEJMoa1917239。Epub 2020 9月20日。
- PubMed ID
-
32955176 (PubMed视图］
- 摘要
-
背景:目前还没有针对癌症KRAS突变的治疗方法被批准。KRAS p.G12C突变发生在13%的非小细胞肺癌(nsclc)和1 - 3%的结直肠癌和其他癌症中。Sotorasib是一种选择性和不可逆靶向KRAS(G12C)的小分子。方法:我们在KRAS p.G12C突变的晚期实体瘤患者中进行了sotorasib的1期试验。患者每日口服一次索托拉西布。主要终点是安全性。主要次要终点为药代动力学和客观缓解，根据实体肿瘤缓解评价标准(RECIST) 1.1版进行评估。结果:共有129例患者(59例非小细胞肺癌，42例结直肠癌，28例其他肿瘤)被纳入剂量递增和扩大队列。患者接受了中位数为3(范围，0到11)的转移性疾病的抗肿瘤治疗。未观察到剂量限制毒性作用或与治疗相关的死亡。 A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma. CONCLUSIONS: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effects occurred in 11.6% of the patients. (Funded by Amgen and others; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).
引用本文的药物库数据
- 药物