PD-1/PD-L1 inhibitor monotherapy or in combination with chemotherapy as upfront treatment for advanced NSCLC with PD-L1 expression ≥ 50%: Selecting the best strategy.

Treatment strategies for advanced NSCLC patients without driver molecular alterations are influenced by PD-L1 expression. If PD-L1 is <50 %, the preferred upfront treatment is the association of chemotherapy and immunotherapy, while immunotherapy alone is an additional option if PD-L1 ≥ 50 %. Both treatments demonstrated their superiority over chemotherapy in this subset of NSCLC patients, with comparable efficacy outcomes but less safety concerns for immunotherapy alone. Nevertheless, a significant difference in terms of early progression-free survival rate emerges by analyzing and comparing the survival curves of the two strategies, reflecting a non-negligible loss of patients due to early disease progression at 3 and 6 months from treatment initiation with immunotherapy alone as compared to its association with chemotherapy. We deeply analyzed efficacy similarities and differences of the two approaches in advanced NSCLC with PD-L1 expression ≥50 %, trying to suggest clinical and biologic aspects to be considered when facing the treatment choice.