Overview
Patients with unresectable stage III non-small cell lung cancer (NSCLC) are treated with the immunotherapy durvalumab after chemoradiation. However, its real-world effectiveness in patients with KRAS G12C mutations, which occur in about 13% of NSCLC cases, remains poorly understood because genetic status was not tracked in the landmark clinical trial. This study used the Flatiron Health Research Database, which includes more than 438,000 patients with NSCLC, to evaluate outcomes for 3,921 eligible patients, including 372 with KRAS G12C-mutant disease. Researchers found that patients with KRAS G12C mutations had similar clinical outcomes on durvalumab compared to patients with other KRAS mutations or wild-type tumors, though more than half of all patients experienced disease progression or death within two years.
Why this matters
As the largest real-world study of its kind, this research confirms that durvalumab consolidation is an active and appropriate treatment for stage III KRAS-mutant NSCLC. However, because over half of these patients still progressed within two years, the findings highlight a clear clinical opportunity to evaluate combining durvalumab with targeted KRAS G12C inhibitors to improve long-term survival outcomes.