The landscape of immune checkpoint inhibitor therapy in advanced lung cancer

Abstract

Background 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. 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. Methods We 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. Results Overall, 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. Conclusion ICI 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.

Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

“…Immune checkpoint inhibitors (ICIs), including anti-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs (such as nivolumab, pembrolizumab, and atezolizumab) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agents (ipilimumab), have become key treatments for patients with advanced or recurrent non-small-cell lung cancer (NSCLC) [ 25 ]. In addition, most patients with advanced NSCLC receive ICIs as a first-line combination chemoimmunotherapy in clinical settings worldwide [ 17 ].…”

Development and validation of a novel nomogram for predicting overall survival of lung cancer patients treated with immune checkpoint inhibitors: A retrospective cohort study in China

“…Now, chemotherapy combined with immunotherapy is the standard treatment for lung cancer, except for patients with high PD-L1 expression(Maung et al 2020). Our ndings indicate that combining chemotherapy with immunotherapy, compared to immunotherapy alone, enhances progression-free survival and OS for patients(Wang et al 2021). D-dimer, a product of brin degradation, re ects brinolysis function.…”

The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer

“…Many studies have shown that they are involved in altering the ability of the immune system to recognize malignant cells. In conditions of immune homeostasis, immune checkpoints provide self-tolerance by maintaining T lymphocyte activation, which causes inhibition of the immune response, but in the case of cancer, they are inhibited and the immune system is reactivated so that it is able to launch an attack on cancer cells [ 350 , 351 ]. In the literature, we found data on the detailed mechanisms of action of almost 20 significant modulators of immune checkpoints ( Table 4 ), such as LAG-3, TIM3 and TIGIT, as well as the programmed cell death receptor 1 (PD-1) and a protein associated with cytotoxic T-4 lymphocytes (CTLA-4) ( Figure 5 ), which have found their greatest application in clinical practice, including the treatment of lung cancer [ 350 , 351 , 352 , 353 , 354 , 355 ].…”

“… Exemplary interactions between a T lymphocyte and a tumor cell and dendritic cell, including immunological checkpoints (based on [ 350 , 351 , 352 , 353 , 354 , 355 ]). …”