First-Line Treatment of Advanced Non-Small-Cell Lung Cancer with Immune-Checkpoint Inhibitors: New Combinations and Long-Term Data

AbstractTreatment of metastatic non-small-cell lung cancers (NSCLCs) has long been based on cytotoxic chemotherapy. Immune checkpoint inhibitors (ICIs), notably monoclonal antibodies directed against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), have transformed therapeutic standards in thoracic oncology. These ICIs are now the reference first-line therapy, and numerous phase III trials have established their efficacy in treatment-na ïve patients. First-line pembrolizumab monotherapy was validated for patients with ≥ 50% of tumor cells expressing PD-L1 and, in the USA, for patients with ≥ 1% PD-L1 positivity. More recently, cemiplimab as monotherapy was also validated for patients whose tumors expressed ≥ 50% PD-L1. Several ICIs (pembrolizumab, atezolizumab, nivolumab, and recently durvalumab) in combination with chemotherapy achieved overall survival gains among “all comers”, compared with chemotherapy alone. The results were more contrasting for paired immunotherapies combining anti-PD-L1 and anti-cytotox ic T-lymphocyte antigen-4 agents, with the benefit/risk balance not yet fully established. Recently, nivolumab–ipilimumab and two chemotherapy cycles limited patient exposure to chemotherapy and obtained positive results compared with the latter alone. However, those phase III trials included sele cted patients in good general condition and without active brain metastases. Little is known about immunotherapy and combination immunotherapy...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research