Background: The KRAS G12C mutation, prevalent in various malignancies, including non-small cell lung cancer (NSCLC), represents a unique therapeutic target. Adagrasib and sotorasib, two FDA-approved agents specifically targeting this mutation, have shown promise in clinical trials. This study aims to compare their efficacy in treating KRAS G12C-mutated NSCLC, drawing insights from pivotal clinical trials.Methods: We analyzed data from three key clinical trials: KRYSTAL-1, CodeBreak100, and CodeBreak200. Our methodology involved reconstructing individual patient data from published Kaplan–Meier curves using the IPDfromKM tool (Version 0.1.10). The primary endpoints were progression-free survival (PFS) and overall survival (OS), evaluated through hazard ratios (HRs) and the restricted mean survival time (RMST) method.Results: The HR for PFS favored adagrasib (HR: 0.90 [95% CI: 0.69, 1.19],p= 0.473), suggesting a non-significant trend toward better disease control compared to sotorasib. For OS, the HR was 0.99 [95% CI: 0.75, 1.33] (p= 0.969), indicating no significant difference between the two drugs. RMST analysis supported these findings, with adagrasib showing a consistently higher RMST in PFS at 6, 12, and 18 months. However, OS benefits converged over time, with adagrasib marginally surpassing sotorasib by the 18-month mark.Conclusions: This comprehensive analysis reveals that while adagrasib may offer a slight advantage in PFS, both drugs demonstrate comparable efficacy in OS for KRAS G12C-mutated NSCLC. The subtle differences observed, particularly in PFS, could inform clinical decision-making, emphasizing the need for personalized treatment strategies. Future research should focus on long-term effects and identifying patient subgroups that may benefit more from one drug over the other.
**背景：** KRAS G12C突变在包括非小细胞肺癌在内的多种恶性肿瘤中普遍存在，是一个独特的治疗靶点。Adagrasib和sotorasib是两种美国食品药品监督管理局批准的、专门靶向该突变的药物，在临床试验中显示出前景。本研究旨在通过分析关键临床试验数据，比较两者在治疗KRAS G12C突变型非小细胞肺癌中的疗效。 **方法：** 我们分析了三项关键临床试验的数据：KRYSTAL-1、CodeBreak100和CodeBreak200。我们的方法涉及使用IPDfromKM工具（版本0.1.10）从已发表的Kaplan-Meier曲线重建个体患者数据。主要终点是无进展生存期和总生存期，通过风险比和限制性平均生存时间方法进行评估。 **结果：** 无进展生存期的风险比倾向于adagrasib（HR: 0.90 [95% CI: 0.69, 1.19], p=0.473），提示与sotorasib相比，adagrasib在疾病控制方面有非显著性的更好趋势。对于总生存期，风险比为0.99 [95% CI: 0.75, 1.33] (p=0.969)，表明两种药物之间无显著差异。限制性平均生存时间分析支持这些发现，adagrasib在6、12和18个月时的无进展生存期限制性平均生存时间持续较高。然而，总生存期获益随时间推移趋于一致，至18个月时adagrasib仅略微超过sotorasib。 **结论：** 这项综合分析表明，虽然adagrasib可能在无进展生存期方面略有优势，但两种药物在KRAS G12C突变型非小细胞肺癌的总生存期方面疗效相当。观察到的细微差异，特别是在无进展生存期方面，可为临床决策提供参考，强调了制定个体化治疗策略的必要性。未来的研究应关注长期疗效，并识别可能从其中一种药物获益更多的患者亚组。
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