Lung cancer in never smokers—the East Asian experience

Approximately one third of all lung cancer patients in East Asia are never-smokers. Furthermore, the proportion of lung cancer in never smokers (LCINS) has been increasing over time. Never-smokers are more often diagnosed with adenocarcinoma in East Asia, a subtype largely defined by oncogenic drivers. In this subgroup of patients, as high as 90% of patients have been found to harbor well-known oncogenic mutations and can be successfully managed with targeted therapies inhibiting specific oncogenic mutant kinases. EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment has been the most important targeted therapy in lung adenocarcinoma from East Asian never-smokers as approximately 70% of these patients have the opportunity to receive EGFR-TKI treatment. Lung squamous cell carcinoma (SQCC) and small cell lung cancer (SCLC) are two common histologic types of smoking-related non-small cell lung cancer (NSCLC). The proportion of never-smokers with SQCC and SCLC in East Asian patients seems to be higher than that in Caucasian patients. Recent studies also suggest that lung SQCC and SCLC in never-smokers may be distinct subtypes. Therefore, better understanding of the biologic characteristics of these subtypes of patients may provide new insights for the treatment. In this review, we will provide an overview of East Asian experience in the treatment of advanced, never-smoking lung cancer, focusing on etiologic factors in the development of LCINS, targeted therapy for never-smokers with adenocarcinoma, distinct characteristics of never-smokers with lung SQCC and SCLC, and the role of immunotherapy in never-smokers with NSCLC.