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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