Durvalumab for the treatment of non-small cell lung cancer

Introduction: In non-small cell lung cancer (NSCLC), immunotherapy is one of today’s most important and ground-breaking systemic treatments, mainly represented by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2. Areas covered: In advanced NSCLC patients, durvalumab has demonstrated activity and acceptable tolerability, particularly with ≥25% PD-L1 tumor expression in the EGFR and ALK wild-type population. However, preliminary data have shown lower efficacy in EGFR mutant and ALK-positive patients. The results from the recent PACIFIC study in locally advanced patients have placed durvalumab as standard of care in consolidation after chemoradiation, leading to Food and Drug Administration (FDA) approval. Expert commentary: Early data suggest promising activity for durvalumab with the CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in combination with other drugs such as platinum-doublet chemotherapy. However, treatment-related toxicity associated with the combinations is an important aspect of the benefit-risk evaluation in the decision-making process. Results of ongoing phase III trials will provide illuminating data to confirm the place of durvalumab in the management of NSCLC patients.