Clinical outcomes and safety profile of adagrasib in KRAS G12C-mutated solid tumors: A single-arm meta-analysis.

Abstract

e20648 Background: KRAS G12C mutations are key oncogenic drivers in multiple solid tumors, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), with limited therapeutic options. Targeting KRAS G12C has historically been challenging. However, 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: A systematic literature search was conducted across PubMed, Embase, Scopus, and Cochrane databases to identify clinical trials and observational studies evaluating Adagrasib’s 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 Standardized Mean Difference (SMD) with a 95% confidence interval (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 objective response rate (ORR) was 40% (95% CI: 30%–51%, I² = 69.2%), partial response (PR) rate was 35% (95% CI: 25%–46%, I² = 68.7%) and stable disease (SD) was 49% (95% CI: 40%–58%, I² = 55.6%). The disease control rate (DCR) was 83% (95% CI: 77%–87%, I² = 0%), reflecting robust tumor response and stabilization. The median duration of response (mDOR) was 5.70 months (95% CI: 4.54–6.86, I² = 1.9%). Safety analysis revealed that 97% (95% CI: 93%–99%, I² = 29.1%) of patients experienced at least one adverse event (AE) of varying grades. Dose reductions (DR) was reported in 45% (95% CI: 19%–74%, I² = 95.7%), highlighting significant variability in tolerability across studies. 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. Commonly reported adverse events. Adverse events Pooled Estimate 95% CI Heterogeneity (I²) % Any adverse event 0.97 0.93–0.99 29.1 Grade ≥ 3 adverse events 0.41 0.18–0.68 94.9 Dysgeusia 0.14 0.10–0.19 0 Anemia 0.23 0.14–0.34 68.5 Vomiting 0.50 0.44–0.56 55.6 QT prolongation 0.18 0.13–0.23 0 Peripheral edema 0.19 0.12–0.29 58.6 Rash 0.14 0.09–0.23 51.2