![]() ![]() Herein, we review the contradictory results of recent phase III trials with immune checkpoint inhibitors in the first-line setting, the potential reasons for such discrepancies, and some of the remaining points of discussion related to the positioning of immune checkpoint inhibitors in the first-line therapy of non-small cell lung cancer.įirst-line platinum-based chemotherapy is the standard of care in the majority of patients with advanced non-small cell lung cancer (NSCLC) without comorbidities and with an optimal performance status this excludes patients with oncogenic driver alterations, such as the epidermal growth factor receptor ( EGFR) mutation (in almost 50% of patients of Asian ethnicity compared to 15% in the Caucasian population ) or the anaplastic lymphoma kinase ( ALK) re-arrangement (in 5% patients independently of ethnicity ), who can be treated with tyrosine kinase inhibitors. ![]() Improved responses have also been reported with the combination of immune checkpoint inhibitors and chemotherapy as the first-line treatment however, this strategy has not yet been validated by phase III trial data and its interplay with PD-L1 status still requires clarification. Given the superior outcome with pembrolizumab as an upfront strategy, PD-L1 status should now be considered a new reflex biomarker to guide first-line treatment in patients with advanced non-small cell lung cancer. Immune checkpoint inhibitors have significantly modified the therapeutic landscape of advanced non-small cell lung cancer in second-line settings, with a more recent advancement in first-line settings. ![]()
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