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Clinical Outcomes and Safety Profile of Adagrasib in KRAS G12C-Mutated Solid Tumors

克拉斯 医学 不利影响 耐受性 内科学 加药 临床试验 肿瘤科 观察研究 癌症 结直肠癌
作者
Osama Ahmad,Shree Rath,Umm E. Shabbar Salma Banatwala,Umama Alam,Md. Rafiqul Islam,Abdul Wahid,Fatima Sajjad,Wajiha Khan,Abbas Gain
出处
期刊:American Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:49 (3): 147-155
标识
DOI:10.1097/coc.0000000000001249
摘要

Objectives: KRAS G12C mutations are key oncogenic drivers in multiple solid tumors. Adagrasib, a selective KRAS G12C inhibitor, has demonstrated promising efficacy and safety in clinical studies. This single-arm meta-analysis comprehensively evaluates key clinical outcomes of Adagrasib, including survival benefits and adverse events, in patients with KRAS G12C-mutant solid tumors. Methods: Literature search was conducted across 4 databases to identify clinical trials and observational studies evaluating Adagrasib performance in patients with KRAS G12C-mutant solid tumors. A single-arm analysis was performed using the inverse variance method in the “meta” package of RStudio. Log Proportion and standardised mean difference (SMD) with a 95% CI were pooled using a random-effects model. Heterogeneity was assessed using I ² statistics. Results: Six studies involving 400 patients were included in our analysis. Adagrasib showed a median overall survival (OS) of 14.74 months (95% CI: 12.06-17.42, I ²=40.4%) and progression-free survival (PFS) of 6.80 months (95% CI: 6.14-7.46, I ²=0%), indicating significant survival benefits. The disease control rate (DCR) was 83%, reflecting robust tumor response and stabilization. Safety analysis revealed that 97% of patients experienced at least one adverse event of varying grades. Conclusions: Adagrasib demonstrated robust efficacy in KRAS G12C-mutant solid tumors, with significant survival benefits and high response rates. However, frequent adverse events and dose modifications, along with variability in response rates, highlight tolerability challenges. Further studies are needed to optimize dosing, improve patient selection, and explore combination strategies to enhance outcomes and minimize unwanted effects.
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