Current advances in the treatment of lung cancer with immune checkpoint inhibitors

ABSTRACT

Lung cancer is the leading cause of cancer-related deaths worldwide despite major advances in platinum-based chemotherapy and targeted therapy based on activating driving mutations. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms in lung cancers. When used as a second-line or later treatment for non-small cell lung cancer (NSCLC), ICIs improve overall survival and exhibit better safety profiles than the standard chemotherapeutic agent, docetaxel. In front-line treatment, ICI monotherapy is significantly associated with improved clinical outcomes and fewer adverse events than platinum-based chemotherapy in patients with advanced NSCLC, who express programmed death-ligand 1 in at least 50% of all tumor cells. Moreover, ICIs combined with platinumbased chemotherapy have become the standard first-line treatment for patients with metastatic NSCLC without sensitizing mutations in the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene, regardless of programmed death-ligand 1 expression. Additionally, maintenance treatment using ICIs has also been demonstrated to improve clinical outcomes in patients with stage III unresectable NSCLC following chemoradiotherapy. Recently, the addition of ICIs to chemotherapy as the first-line treatment for extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival compared with chemotherapy alone. Although immune checkpoint inhibitors significantly improved overall survival and showed a durable response in lung cancer compared with platinum-based chemotherapy, we should foster further prospective studies to identify predictive biomarkers to determine those individuals who may benefit more from ICIs. It is also essential to overcome the development of drug resistance in patients treated with ICIs.