METHODS: We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest.
RESULTS: 18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRASG12C-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77).
CONCLUSIONS: This study provided a comprehensive understanding of the efficacy and safety of KRASG12C inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRASG12C inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRASG12C inhibitor treatment.
方法:我们搜索了PubMed,EMBASE,科克伦图书馆,以及截至2023年3月6日以英文发表的主要国际临床试验会议。临床试验调查索托拉西或阿达格拉西布,并报告客观反应率(ORR)的临床结果,疾病控制率(DCR),或≥3级不良事件(AEs)的发生率合格.主要终点是ORR。次要终点包括DCR,≥3级不良事件发生率,以及有或没有共突变的患者之间ORR的比值比(OR)。随机效应模型应用于感兴趣的结果。
结果:本荟萃分析纳入了18项研究,共1224例患者。汇集的ORR,DCR,≥3级不良事件发生率为31%(95%CI,25%-37%),86%(95%CI,82%-89%),和29%(95%CI,23%-36%),分别。具有KEAP1共突变的KRASG12C突变的NSCLC患者表现出比具有野生型KEAP1的患者更差的ORR(OR:0.35,95%CI:0.16-0.76)。
结论:本研究全面了解了KRASG12C抑制剂治疗实体肿瘤的有效性和安全性,并确定了KEAP1突变作为KRASG12C抑制剂治疗患者低反应的潜在预测生物标志物。这些发现可能有助于设计未来的临床试验,以确定可能受益于KRASG12C抑制剂治疗的人群。