Clinical Outcomes and Safety Profile of Adagrasib in KRAS G12C-Mutated Solid Tumors: A Single-Arm Meta-Analysis.

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 I² 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, I²=40.4%) and progression-free survival (PFS) of 6.80 months (95% CI: 6.14-7.46, I²=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.