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Potency and Safety of KRAS G12C Inhibitors in Solid Tumors: A Systematic Review

Sara El Zaitouni1, Abdelilah Laraqui2, Youssra Boustany3

  • 1Laboratory of Biology of Human Pathologies, Genomic Center of Human Pathologies, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco.

Clinical Medicine Insights. Oncology
|April 29, 2025
PubMed
Abstract

Insights

KRAS G12C inhibitors like Sotorasib and Adagrasib show significant clinical benefits in solid tumors. These targeted therapies improve objective response rates and survival outcomes in patients with KRAS G12C-mutated cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Clinical Pharmacology

Background:

  • The Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation is a key driver in various solid tumors.
  • KRAS G12C inhibitors represent a novel therapeutic strategy for patients with KRAS-mutated cancers.
  • Understanding the efficacy and safety of these inhibitors is crucial for clinical application.

Purpose of the Study:

  • To comprehensively evaluate the effectiveness and toxicity of KRAS G12C inhibitors.
  • To compare the outcomes of Sotorasib, Adagrasib, Garsorasib, and Divarasib in specific solid tumors.
  • To assess treatment responses and survival benefits in colorectal cancer, non-small-cell lung cancer, and pancreatic ductal adenocarcinomas.

Main Methods:

  • Systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
  • Inclusion of clinical trials data from January 2020 to August 2023.
  • Searches conducted across PubMed, EMBASE, Cochrane Library, and major international conferences.

Main Results:

  • Seventeen eligible studies were analyzed, with Sotorasib and Adagrasib featuring in the most trials.
  • Sotorasib demonstrated significant objective response rates (ORR), progression-free survival (PFS), and overall survival (OS), particularly in non-small-cell lung cancer (NSCLC).
  • Adagrasib showed comparable or superior efficacy to Sotorasib in pancreatic ductal adenocarcinomas (PDAC) and NSCLC, while both drugs showed moderate efficacy in colorectal cancer (CRC).

Conclusions:

  • KRAS G12C inhibitors, alone or with conventional therapies, enhance treatment responses in solid tumors.
  • These inhibitors effectively modulate tumor progression in patients with KRAS G12C mutations.
  • The findings support the clinical utility of KRAS G12C inhibitors in treating specific cancer types.
Keywords:
KRAS G12C inhibitorsKRAS G12C mutationcolorectal cancernon-small cell lung cancerpancreatic ductal adenocarcinoma

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