Anti-PD-(L)1 therapy of non-small cell lung cancer-A summary of clinical trials and current progresses

This review discusses the impact of mono or combination therapy of immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) patients, comparing clinical outcomes and safety. Cancer subtype, tumor mutational burden (TMB), programmed death-ligand 1 (PD-L1) expression state and T cell infiltration (TIL) density are considered for interpretations. Besides, current progresses in the field of immunotherapy are discussed.

Anti-PD-(L)1 is a safe and an effective strategy in patients with advanced/metastatic NSCLC. Clinical responses to nivolumab and pembrolizumab, in particular, are promising. The most desired clinical responses are for patients receiving combination of anti-PD-(L)1 or anti-PD-(L)1/anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) with chemotherapy (taxane and platinum). PD-L1 expression state (PD-L1 ≥ 50%), patient performance state (PS: 0-1 ECOG scale) and effector T cell (Teff) immune signature considerably affect ICI responses. Higher ICI responses are also expected in TMB ^high but EGFR^-/ALK^- cancer patients. In regard with safety profile, adverse events (AEs) related to anti-PD-(L)1 are lower compared with that for platinum-based and docetaxel therapy. Toripalimab is the safest among various immunotherapy drugs. Bispecific antibodies against anti-PD-(L)1 with dominant signaling or alternative checkpoints in tumor microenvironment (TME) is the current focus in immunotherapy of cancers like NSCLC. Besides, the contribution of extracellular vesicles (EVs) to immune escape and their implication in cancer diagnosis and therapy is on the eye of current investigations.

Appropriate biomarker selection will improve therapy outcomes in ICI treated NSCLC patients, particularly in cases under combinatory ICI therapy. Application of bispecific antibodies and EV-based targeted therapy are effective novel strategies to improve therapeutic outcomes in cancer patients.