Abstract：
UNASSIGNED: To evaluate the safety and efficacy of the novel KRAS-targeting agents, sotorasib and adagrasib, in treating KRAS G12C-mutated non-small cell lung cancer (NSCLC).
UNASSIGNED: A comprehensive English-based literature search of PubMed and Clinicaltrials.gov between January 2000 and July 2023 was conducted using the terms sotorasib, Lumakras, AMG 510, adagrasib, Krazati, and MRTX849.
UNASSIGNED: Relevant prescribing information, clinical trials, and treatment guidelines were evaluated.
UNASSIGNED: Sotorasib and adagrasib received accelerated US Food and Drug Administration (FDA) approval following pivotal phase I/II clinical trials. Sotorasib, a first-in-class KRAS inhibitor, demonstrated an overall response rate (ORR) of 41% and a progression-free survival (PFS) of 6.3 months. In a phase III confirmatory trial, sotorasib showed significantly longer PFS compared with docetaxel (5.6 vs. 4.5 months; P = 0.0017). Adagrasib produced an ORR of 42.9% and a PFS of 6.5 months. Both drugs present unique safety profiles, with common toxicities, including diarrhea, musculoskeletal pain, fatigue, and hepatotoxicity.
UNASSIGNED: With KRAS mutations being among the most common oncogenic alterations in NSCLC, sotorasib and adagrasib offer new therapeutic avenues for this previously \"undruggable\" target. Current treatment guidelines list sotorasib and adagrasib as second-line options in patients with confirmed KRAS G12C-mutated NSCLC. Additional studies are required to further differentiate the safety and efficacy profiles of these 2 agents and identify their optimal place in therapy.
UNASSIGNED: Sotorasib and adagrasib demonstrated promising outcomes in targeting the constitutively active KRAS G12C oncogenic driver, underscoring the need for further research to optimize their therapeutic application in this high-risk population.
UNASSIGNED: A comprehensive English-based literature search of PubMed and Clinicaltrials.gov between January 2000 and July 2023 was conducted using the terms sotorasib, Lumakras, AMG 510, adagrasib, Krazati, and MRTX849.
UNASSIGNED: Relevant prescribing information, clinical trials, and treatment guidelines were evaluated.
UNASSIGNED: Sotorasib and adagrasib received accelerated US Food and Drug Administration (FDA) approval following pivotal phase I/II clinical trials. Sotorasib, a first-in-class KRAS inhibitor, demonstrated an overall response rate (ORR) of 41% and a progression-free survival (PFS) of 6.3 months. In a phase III confirmatory trial, sotorasib showed significantly longer PFS compared with docetaxel (5.6 vs. 4.5 months; P = 0.0017). Adagrasib produced an ORR of 42.9% and a PFS of 6.5 months. Both drugs present unique safety profiles, with common toxicities, including diarrhea, musculoskeletal pain, fatigue, and hepatotoxicity.
UNASSIGNED: With KRAS mutations being among the most common oncogenic alterations in NSCLC, sotorasib and adagrasib offer new therapeutic avenues for this previously \"undruggable\" target. Current treatment guidelines list sotorasib and adagrasib as second-line options in patients with confirmed KRAS G12C-mutated NSCLC. Additional studies are required to further differentiate the safety and efficacy profiles of these 2 agents and identify their optimal place in therapy.
UNASSIGNED: Sotorasib and adagrasib demonstrated promising outcomes in targeting the constitutively active KRAS G12C oncogenic driver, underscoring the need for further research to optimize their therapeutic application in this high-risk population.
摘要：
■为了评估新型KRAS靶向药物的安全性和有效性，sotorasib和adagrasib,用于治疗KRASG12C突变的非小细胞肺癌（NSCLC）。
■在2000年1月至2023年7月之间对PubMed和Clinicaltrials.gov进行了全面的英文文献检索，使用术语sotorasib，卢马克拉斯,AMG510,Adagrasib,Krazati,MRTX849
■相关处方信息，临床试验,和治疗指南进行了评估。
■Sotorasib和adagrasib在关键的I/II期临床试验后获得了美国食品和药物管理局（FDA）的加速批准。Sotorasib,一流的KRAS抑制剂,总缓解率(ORR)为41%,无进展生存期(PFS)为6.3个月.在第三阶段验证试验中，与多西他赛相比，索托拉西布显示出明显更长的PFS（5.6vs.4.5个月；P=0.0017）。Adagrasib产生42.9%的ORR和6.5个月的PFS。两种药物都具有独特的安全性，具有常见的毒性，包括腹泻,肌肉骨骼疼痛，疲劳,和肝毒性。
■KRAS突变是NSCLC中最常见的致癌改变之一，sotorasib和adagrasib提供了新的治疗途径为这个以前的“不可用的”目标。目前的治疗指南将索托拉西和阿达格拉西布列为确诊的KRASG12C突变NSCLC患者的二线选择。需要进一步的研究来进一步区分这两种药物的安全性和有效性，并确定它们在治疗中的最佳位置。
■Sotorasib和adagrasib在靶向组成型活性KRASG12C致癌驱动因素方面表现出了有希望的结果，强调需要进一步研究以优化其在这一高风险人群中的治疗应用。
■在2000年1月至2023年7月之间对PubMed和Clinicaltrials.gov进行了全面的英文文献检索，使用术语sotorasib，卢马克拉斯,AMG510,Adagrasib,Krazati,MRTX849
■相关处方信息，临床试验,和治疗指南进行了评估。
■Sotorasib和adagrasib在关键的I/II期临床试验后获得了美国食品和药物管理局（FDA）的加速批准。Sotorasib,一流的KRAS抑制剂,总缓解率(ORR)为41%,无进展生存期(PFS)为6.3个月.在第三阶段验证试验中，与多西他赛相比，索托拉西布显示出明显更长的PFS（5.6vs.4.5个月；P=0.0017）。Adagrasib产生42.9%的ORR和6.5个月的PFS。两种药物都具有独特的安全性，具有常见的毒性，包括腹泻,肌肉骨骼疼痛，疲劳,和肝毒性。
■KRAS突变是NSCLC中最常见的致癌改变之一，sotorasib和adagrasib提供了新的治疗途径为这个以前的“不可用的”目标。目前的治疗指南将索托拉西和阿达格拉西布列为确诊的KRASG12C突变NSCLC患者的二线选择。需要进一步的研究来进一步区分这两种药物的安全性和有效性，并确定它们在治疗中的最佳位置。
■Sotorasib和adagrasib在靶向组成型活性KRASG12C致癌驱动因素方面表现出了有希望的结果，强调需要进一步研究以优化其在这一高风险人群中的治疗应用。
