Abstract 4117: Clinicopathologic and molecular characterization of KRASG12D lung cancers

Introduction: Allele-specific KRAS inhibitors are an emerging class of cancer therapies. KRASmut non-small cell lung cancers (NSCLCs) exhibit heterogenous outcomes, driven by differences in underlying biology shaped by co-mutations. In contrast to KRASG12C NSCLC, KRASG12D NSCLC is associated with low/never smoking status and has not been characterized in depth. Methods: We examined characteristics of patients with advanced KRASmut NSCLC seen at a single center. RECISTv1.1 and Cox-proportional hazards models adjusting for line of therapy and performance status were used to compare outcomes to immunotherapy. Benjamini-Hochberg corrected q-values were used for genomic comparisons. Results: Of 1,823 patients with KRASmut NSCLC, 16% (n=283) harbored KRASG12D which was mutually exclusive from other targetable alterations. Among these, the median age was 66 (range 20-92), 0.7% had squamous histology, 30% had a never/light smoking history (