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Review
. 2021 Feb 5:10:9-26.
doi: 10.2147/ITT.S253581. eCollection 2021.

Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?

Francesco Passiglia  1 , Maria Lucia Reale  1 , Valeria Cetoretta  1 , Silvia Novello  1
Affiliations
Review

Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?

Francesco Passiglia et al. Immunotargets Ther. .

Abstract

The therapeutic targeting of the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis marked a milestone in the treatment of non-small cell lung cancer (NSCLC), leading to unprecedented response duration and long-term survival for a relevant subgroup of patients affected by non-oncogene-addicted, metastatic disease. However, the biological heterogeneity as well as the occurrence of innate/acquired resistance are well-known phenomena which significantly affect the therapeutic response to immunotherapy. To date, we are moving towards the second phase of the "immune-revolution", characterized by the advent of new immune-checkpoint inhibitors combinations, aiming to target the main resistance pathways and ultimately increase the number of NSCLC patients who may derive long-term clinical benefit from immunotherapy. In this review, we provide an updated and comprehensive overview of the main PD-1/PD-L1 inhibitors' combination approaches under clinical investigation in non-oncogene addicted, metastatic NSCLC patients, including checkpoints (other than CTLA-4) as well as "immune-metabolism" modulators, DNA repair pathway inhibitors, antiangiogenic agents, cytokines, and a new generation of vaccines, with the final aim of identifying the most promising options on the horizon.

Keywords: PD-1/PD-L1; combinations; immune-checkpoint; non-small cell lung cancer; resistance.

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Conflict of interest statement

Francesco Passiglia declared consultant’s fee from MSD, Astra Zeneca, Boehringer Ingelheim, BMS and Pfizer. Maria Lucia Reale declared consultant’s fee from Eli Lilly. Silvia Novello declared speaker bureau/advisor’s fee from Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Astra Zeneca and Boehringer Ingelheim. The authors have no other conflict of interest to declare.

Figures

Figure 1
Figure 1
Immune-checkpoint inhibitors combinations in non-oncogene addicted advanced NSCLC.
See this image and copyright information in PMC

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