1484P - Impact of concomitant KRAS/STK11 or KRAS/KEAP1 mutations on response to immune checkpoint inhibition in NSCLC: A real-world data analysis

Background

STK11 and KEAP1 mutations are among the most common gene alterations in lung adenocarcinoma and are associated with poor response to immunotherapy in patients with KRAS mutations. There is limited data on the clinical relevance of these alterations in a real-world setting.

Methods

Clinicopathologic and genomic data from patients with advanced lung cancer who underwent tissue-based panel next-generation sequencing (NGS) analysis, using the FoundationOne CDX assay, between January 2021 and February 2023 were retrospectively analyzed. Clinical outcomes were evaluated based on the molecular alterations and co-alterations that occurred.

Results

Of 100 patients (median age = 68 y [range: 40-92]), 51 women (51%), 39 smokers (39%), KRAS mutations were detected in 25 cases (25%), STK11 in 12 (12%) and KEAP1 mutations were found in 7 (7%) patients (pts.), respectively. Further alterations were EGFR exon 18-21 in 12 patients (12%), BRAF p.V600E in 3 pts. (3%), ERBB2 ampl. 3 pts. (3%), ALK fusion in 2 pts. (2%), ROS fusion 1 (1%), MET exon 14 skipping mutation in 2 pts. (2%), ERBB2 mutation in 1 pts. (1%), EGFR exon 20 insertion in 1 pts. (1%). In 5 patients (5%) concomitant KRAS/STK11 mutations were detected. One patient showed KRASwt with concominant STK11 mutation. Concomitant KRAS/KEAP1 mutations were detected in 2 patients (2%). None of the patients with STK11 or KEAP1 mutations had concurrent EGFR mutations in exon 18-21, ALK fusions, or ROS fusions.

Conclusions

Therapeutically relevant gene variants were detected in the analyzed real world population. The data indicate that STK11 or KEAP1 mutations should be interpreted in the context of KRAS mutations and could serve as a clinical biomarker for poor response to immunotherapy in patients with lung adenocarcinomas. In addition, the data highlight the benefit of panel sequencing that includes the STK11 and KEAP1.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Louisa Hempel.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.