Abstract
The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results that led to their approval in clinical practice. However, there is limited evidence on immunotherapy rechallenge after recurrence, with the majority of available knowledge coming from retrospective studies which involve heavily pretreated patients with advanced NSCLC. The recent introduction in the curative setting and the potential regulatory restrictions raise questions about the optimal choice of first-line and subsequent therapies for patients with systemic relapse. The role of immunotherapy readministration in this new scenario needs to be clarified, as well as the identification of patients for whom it is more appropriate, including clinical characteristics, duration of response, switching to other ICIs, reasons for discontinuation and immune-related toxicity. Here, we review literature on rechallenge with immunotherapy, including efficacy, safety profile and potential predictive factors of response.