Immune checkpoint inhibitors in non-small-cell lung cancer: current status and future directions

Abstract

Since 2015, immunotherapies, especially immune checkpoint inhibitors (ICIs), have made great breakthroughs in non-small-cell lung cancer (NSCLC). Among them, nivolumab, pembrolizumab and atezolizumab have been granted US Food and Drug Administration approval for NSCLC. It is imperative to combine ICIs with chemotherapy, radiotherapy, antivascular therapy and targeted therapy. But in the bright future, there are two problems. One is how to use biomarkers to select the beneficiaries. The other is how to achieve a balance between drug effectiveness and safety. There are now seven drugs targeting the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways that have been or are expected to enter clinical treatment. This review focuses on these drugs and summarizes clinical trials that have been reported or that ongoing ones have already entered the recruiting state.

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

“…Representing 80-85% of all cases of lung cancer, non-smallcell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide [1]. Over the course of the last decade, the prognosis improved drastically, in large part thanks to the advent of immune checkpoint inhibitors (ICIs) [2,3].…”

Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Carcinoma Biopsies and Its Association with Tumor Infiltrating Lymphocytes and the Degree of Desmoplasia

“…Inhibítory imunitných kontrolných bodov, ktoré blokovaním inhibičnej signálnej dráhy PD-1/ PD-L1 (programmed death-1 / programmed death-ligand 1) vedú k reaktivácii potlačeného imunitného systému, výrazne zlepšili prognózu pa cientov s lokálne pokročilým a metastazujúcim NSCLC [3,4]. V súčasnosti sú pre klinické používanie v európskych krajinách schválené anti-PD-1 protilátky nivolumab a pembrolizumab a anti-PD-L1 protilátky atezolizumab, avelumab a durvalumab [5,6].…”

Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment

“…In recent years, there is increasing emphasis on enhancing the anti-tumor immune response thru use of immune-checkpoint blockade (ICB) [ 13 ]. While this strategy has impacted outcomes considerably in non-small cell lung cancer (NSCLC) [ 14 ], melanoma [ 15 ] and other malignancies [ 16 ], it has a lesser impact in CRC [ 17 ]. Understanding how 5-FU chemotherapy regimens affect the anti-tumor immune response in CRC is critical to devising new ways to harness the immune system to improve outcomes for CRC patients.…”