Rechallenge with immune-checkpoint inhibitors in patients with advanced-stage lung cancer

Abstract

Lung cancer remains the leading cause of cancer-related mortality globally, with many patients diagnosed with advanced-stage disease. Treatment in this setting relies on systemic therapies, including chemotherapy, targeted therapy and immunotherapy. Immune-checkpoint inhibitors (ICIs), which promote or restore antitumour immunity by inhibiting immunosuppressive signalling pathways, are currently the most widely used immunotherapies in these patients. However, immune-related adverse events (irAEs) or disease progression often necessitate discontinuation of these agents, leaving many patients with limited subsequent treatment options. In this scenario, ICI rechallenge has emerged as a potential strategy. Despite this potential, evidence for ICI rechallenge after either disease progression or irAEs in patients with non-small-cell lung cancer is limited and evidence for those with small cell lung cancer seems to be non-existent. In this Review, we provide a comprehensive overview of the available data on ICI rechallenge in the context of both disease progression and irAEs, including a summary of current guidance on clinical management and detailed discussions of safety and efficacy. We also highlight important unanswered questions in an attempt to guide future research in this area.

Patients with advanced-stage lung cancer might discontinue immune-checkpoint inhibitor (ICI) treatment for various reasons, including toxicities, disease progression or disease remission. Nonetheless, treatment options in this setting are often limited and some patients might derive benefit from re-administration of a previously received ICI. In this Review, the authors summarize the available data on ICI rechallenge, including the reasons for discontinuation and the feasibility of rechallenge in various clinical scenarios, and highlight important unaddressed research questions.