KRAS^G12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia

Simple Summary: Interstitial pneumonia (IP) represents a significant prognostic comorbidity in patients diagnosed with non-small-cell lung cancer (NSCLC). Even if treatment for lung cancer proves effective, the occurrence of an acute exacerbation in pre-existing IP can pose a substantial risk to patient survival. Consequently, it is crucial to opt for a therapy that minimizes the likelihood of triggering an acute IP exacerbation. Evidence is limited regarding pharmacotherapy for advanced NSCLC with a low risk of triggering the exacerbation of pre-existing IP, but KRAS(G12C) inhibitors may be a potential treatment option for NSCLC with comorbid IP. In this review article, we discuss the promise and prospects of molecular-targeted therapy, particularly KRAS(G12C) inhibitors, which gained little attention as a treatment for NSCLC with comorbid IP. Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRAS(G12C) mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRAS(G12C) inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRAS(G12C) inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRAS(G12C) inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.