OncoTargets and Therapy (Sep 2020)
Primary Resistance to Immune Checkpoint Blockade in an STK11/TP53/KRAS-Mutant Lung Adenocarcinoma with High PD-L1 Expression
Abstract
Won Gun Kwack,1 So Youn Shin,2 Seung Hyeun Lee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea; 2Department of Radiology, Kyung Hee University School of Medicine, Seoul, South KoreaCorrespondence: Seung Hyeun LeeDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Kyungheedae-ro 23, Dongdaemun-gu, Seoul 02447, South KoreaTel +82 2 958 8511Fax +82 2 968 1848Email [email protected]: Several studies have shown that STK11 and TP53 mutations have different effects on the susceptibility to immune checkpoint blockade in KRAS-mutant non-small cell lung cancer (NSCLC). However, the impact of STK11/TP53 co-mutations on treatment outcomes in the same clinical setting has never been reported. We recently encountered a case of a 70-year-old man who was diagnosed with advanced lung adenocarcinoma with high-programmed death-ligand 1 (PD-L1) expression. He received pembrolizumab monotherapy as a frontline treatment; however, the tumor did not respond to this therapy and showed deleterious outcome. Next-generation sequencing revealed that the tumor harbored a rare STK11/TP53/KRAS triple mutation. Our case suggests that these compound mutations may constitute a distinct, aggressive subset that is resistant to immunotherapy even when the tumor strongly expresses PD-L1. In addition, this report highlights the importance of using molecular profiling to detect co-mutations that can be associated with primary resistance or disease progression to improve survival even in the immunotherapy setting.Keywords: lung cancer, KRAS, STK11, TP53, immune checkpoint inhibitors, prognosis
