The landscape of immune checkpoint inhibitor therapy in advanced lung cancer

Chengdi Wang,Qiran Zhang,Jiayang Wu,Hanlin Gong,Yalun Li,Lujia Song,Yuxuan Xiao,Jingwei Li

doi:10.1186/s12885-021-08662-2

Chengdi Wang, Qiran Zhang + Show 6 more

Open Access

https://doi.org/10.1186/s12885-021-08662-2

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Abstract

BackgroundThe advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.MethodsWe identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.ResultsOverall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70–0.79] and [HR = 0.82; 95% CI, 0.75–0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.ConclusionICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

Highlights

Lung cancer is the primary cause of cancer-related mortality and incidence, resulting in a significant economic burden [1]
We used published data from 38 Randomised controlled trial (RCT) of high quality, including more than 20,000 patients with lung cancer, revealing that Immune checkpoint inhibitor (ICI) were associated with a better therapeutic effect on reducing the risk of death in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) without increasing Treatment-related adverse events (TRAEs) when compared with Standard of care (SOC)
Among the treatment strategies, ICIs plus SOC led to a better improvement in progression-free survival (PFS) than ICI monotherapy in both patients with NSCLC and SCLC patients; it is recommended for patients with advanced lung cancer as a preferential option

Summary

Introduction

Lung cancer is the primary cause of cancer-related mortality and incidence, resulting in a significant economic burden [1]. SCLC accounts for only 15% of lung cancers, with first-line treatment mainly restricted to chemotherapy or radiotherapy and presenting a worse prognosis than NSCLC [2]. NSCLC constitutes approximately 85% of lung cancers and presents a relatively superior prognosis, given the rapid development of therapeutic techniques, including surgery, chemotherapy, radiotherapy, and targeted therapy [3, 4]; the actual 5-year overall survival (OS) of NSCLC remains poor. Immune checkpoint inhibitors (ICIs) developed to treat malignant tumours, including lung cancer, can be classified into anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies. The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. We aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types

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