Treatment of Advanced Non–Small-Cell Lung Cancer: From Chemotherapy to Chemoimmunotherapy

Patients with advanced non–small-cell lung cancer (NSCLC) are currently treated with chemotherapy, targeted therapies, and immunotherapy. In their article, Bodor et al1 summarize the current status of first-line therapies for patients with metastatic lung adenocarcinomas without driver mutations. Approximately three decades ago, palliative chemotherapy of advanced NSCLC became generally accepted in routine clinical practice. This was largely based on results from a meta-analysis of randomized trials that demonstrated a survival benefit for platinum-based chemotherapy over best supportive care alone1 and the availability of better antiemetics, which resulted in improved tolerance of chemotherapy. Several third-generation cytotoxic drugs with improved efficacy and/or tolerability then entered clinical practice. Platinum-based doublets that contained one of these cytotoxic drugs were established as standard treatment of patients with good performance status, and single agents or well-tolerated doublets were established as standards for both elderly patients and selected patients with reduced performance status. Next, therapeutic strategies focused on inhibition of angiogenesis or growth factor receptors (for review, see Pirker and Filipits2). Bevacizumab added to platinum-based doublets was established as standard for patients with advanced nonsquamous NSCLC. The epidermal growth factor receptor (EGFR) was targeted by monoclonal antibodies and tyrosine kinase inhibitors. Chemotherapy plus an EGFR monoclonal antibody improved overall survival and, in my opinion, is a treatment option particularly for patients with squamous cell NSCLC and high EGFR expression or EGFR positivity by fluorescence in situ hybridization.3 EGFR mutations and other driver mutations were characterized.2 This led to molecular analyses of tumors in routine practice and treatment of patients with driver mutations with corresponding tyrosine kinase inhibitors. Although the percentage of driver mutation–positive lung cancers will probably further increase in the future, the majority of worldwide patients will continue to be diagnosed with cancers without documented driver mutations. The clinically most relevant therapeutic advance since the implementation of palliative chemotherapy has been the recent establishment of immune checkpoint inhibitors as standard treatment of patients with advanced NSCLC. This opinion is based on three facts. First, the majority of worldwide patients and probably > 80% of patients in the Western world are candidates for treatment with these drugs. Second,