Choosing the optimal immunotherapeutic strategies for non-small cell lung cancer based on clinical factors

The treatment landscape of advanced non-small cell lung cancer (NSCLC) has changed dramatically since the emergence of immune checkpoint inhibitors (ICIs). Although some patients achieve long survival with relatively mild toxicities, not all patients experience such benefits from ICI treatment. There are several ways to use ICIs in NSCLC patients, including monotherapy, combination immunotherapy, and combination chemoimmunotherapy. Decision-making in the selection of an ICI treatment regimen for NSCLC is complicated partly because of the absence of head-to-head prospective comparisons. Programmed death-ligand 1 (PD-L1) expression is currently considered a standard biomarker for predicting the efficacy of ICIs, although some limitations exist. In addition to the PD-L1 tumor proportion score, many other clinical factors should also be considered to determine the optimal treatment strategy for each patient, including age, performance status, histological subtypes, comorbidities, status of oncogenic driver mutation, and metastatic sites. Nevertheless, evidence of the efficacy and safety of ICIs with some specific conditions of these factors is insufficient. Indeed, patients with poor performance status, oncogenic driver mutations, or interstitial lung disease have frequently been set as ineligible in randomized clinical trials of NSCLC. ICI use in these patients is controversial and remains to be discussed. It is important to select patients for whom ICIs can benefit the most from these populations. In this article, we review previous reports of clinical trials or experience in using ICIs in NSCLC, focusing on several clinical factors that are associated with treatment outcomes, and then discuss the optimal ICI treatment strategies for NSCLC.