Abstract
In the past two decades, there have been rapid advances in the number and range of regulatory approvals of targeted therapy for patients with advanced non-small cell lung cancer (NSCLC) and other cancers. The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has a high mutation rate in human cancers and is associated with some of the most aggressive types of cancer, including NSCLC, pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC). Until recently, several common and highly aggressive cancers with KRAS mutations expressing the 'death star' KRAS proteins were considered 'undruggable' and not amenable to targeted therapy. The main KRAS mutations are single-base missense mutations, with 98% occurring at codon 12 (G12C). KRAS G12C is the most common KRAS mutation in NSCLC. Sotorasib is a first-in-class specific small molecule that irreversibly inhibits KRAS G12C. Based on the results from the phase 1/2 CodeBreaK 100 safety and tolerability study, on May 28, 2021, the US Food and Drug Administration (FDA) granted accelerated approval for sotorasib for adults with advanced NSCLC and KRAS G12C mutation. This Editorial aims to present the current status of regulatory approval and the supporting clinical trial data for sotorasib, the first targeted therapy for patients with advanced NSCLC with the KRAS G12C mutation.