Immune checkpoints inhibitors rechallenge in non-small-cell lung cancer: different scenarios with different solutions?

摘要

In recent years, the oncologic community has witnessed a revolution in the treatment of patients with advanced non-small-cell lung cancer (NSCLC) and no actionable mutations [1]. For these patients, unleashing the immune response against cancer with the specific use of immune checkpoint inhibitors (ICIs) aimed at blocking the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) has resulted into a dramatic improvement of overall prognosis. Recent data also suggest that, depending on the levels of PD-L1 expression on tumor cells, first-line therapy with an ICI, with or without cytotoxic chemotherapy, is associated with improved clinical outcome as compared with chemotherapy alone [2–4]. However, several questions still need to be addressed with regards to the optimal implementation of immunotherapy into routine clinical practice. First, it is still uncertain what is the value of adding cytotoxic chemotherapy to an ICI in patients with high PD-L1 expression (≥50%) on tumor cells; second, there is an urgent need for biomarkers more reliable than PD-L1 expression for selection of patient candidates to immunotherapy; third, it is unknown what should be the optimal duration of ICIs treatment.