Outcomes with KRAS G12C inhibitors in metastatic non-small cell cancer: A systematic review and meta-analysis.

Abstract

e20647 Background: KRAS G12C inhibitors have been approved for treating metastatic non-small lung cell carcinoma (mNSCLC) in patients who have received at least one prior systemic therapy. However, past studies have not shown consistent results. This meta-analysis aimed to assess the outcomes of KRAS G12C inhibitors in mNSCLC. Methods: A comprehensive literature search was performed on PubMed, Cochrane, and Clinicaltrials.gov, and after screening of 192 articles, four studies reporting outcomes of KRAS G12C inhibitors in mNSCLC were included. Inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% confidence Interval (CI) was extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2). Results: A total of 772 patients from four studies (2021-2024) included for the analysis. The median age was 64 (32-88) years and majority were male (54%, n=255/471). Two of the included studies were Phase III and rest were Phase I/II. Sotorasib 61% (n=471) and adagrasib 39% (n=301) were used KRAS G12C inhibitors. The median number of prior therapies was 2 (1-3) and most used regimen was either platinum-based chemotherapy or PD-L1 inhibitors. The median follow-up was 15.3 (1.1-18.4). The pooled progression-free survival (PFS) and overall survival (OS) was 41% (95% CI 0.37-0.46, I 2 =94%, p<0.01, n=469) and 49.9% (95% CI 0.45-0.54, I 2 =0%, p=1.00, n=469) at the median follow-up of 6 and 12 months, respectively. The pooled overall response rate (ORR) was 33.8% (95% CI 0.30-0.37, I 2 =59%, p=0.06, n=770) while the median duration of response was 9.85 (7.1-18) months. The pooled adverse events (AE) rate was 52.9% (95% CI 0.49-0.56, I 2 =96%, p<0.01, n=772). Diarrhea was the most commonly reported adverse event (22%, n=73/345) followed by ALT (13%, n=44) and AST elevation (12%, n=40). Conclusions: KRAS G12C inhibitors displayed favorable efficacy with acceptable safety profile in the 2nd of later line of therapies. It is the need of an hour to study this targeted therapy in the first line in mNSCLC patients.