scholarly journals Immune-related pneumonitis associated with immune checkpoint inhibitors in lung cancer: a network meta-analysis

2020 ◽  
Vol 8 (2) ◽  
pp. e001170
Author(s):  
Xinru Chen ◽  
Zhonghan Zhang ◽  
Xue Hou ◽  
Yaxiong Zhang ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Lower Risk ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Increased Risk ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically revolutionized lung cancer treatment, providing unprecedented clinical benefits. However, immune-related pneumonitis (IRP) caused by ICIs has aroused widespread concern due to its high rate of discontinuation and mortality. This network meta-analysis (NMA) aims to compare the risks of IRP among different regimens for advanced lung cancer.MethodsPhase II and III randomized clinical trials (RCTs) were searched from electronic databases. The rates of grade 1–5 IRP and grade 3–5 IRP were systematically extracted. An NMA was conducted among chemotherapy, ICIs monotherapy, dual ICIs combination, and ICIs+chemotherapy. Subgroup analysis was also compared based on specific types of ICIs.ResultsTwenty-five RCTs involving 17,310 patients were eligible for inclusion. Compared with chemotherapy, ICI-based regimens were associated with an increased risk of grade 1–5 IRP and grade 3–5 IRP. Compared with ICIs+chemotherapy, ICIs monotherapy (grade 1–5: OR 2.14, 95% credible interval 1.12 to 4.80; grade 3–5: 3.03, 1.491 to 6.69) and dual ICIs combination (grade 1–5: 3.86, 1.69 to 9.89; grade 3–5: 5.12, 2.01 to 13.68) were associated with a higher risk of grade 1–5 IRP and grade 3–5 IRP. No significant difference was found between dual ICIs combination and ICIs monotherapy in grade 1–5 IRP (1.85, 0.91 to 3.37) or in grade 3–5 IRP (1.65, 0.81 to 3.37). Besides, compared with programmed cell death protein 1 (PD-1) inhibitors (2.56, 1.12 to 6.60), a lower risk of grade 1–5 IRP was observed in programmed cell death ligand 1 (PD-L1) inhibitors.ConclusionCompared with chemotherapy, using ICIs is associated with an increased risk of IRP. ICIs+chemotherapy is associated with a lower risk of IRP compared with dual ICIs combination and ICIs monotherapy. PD-1 inhibitors are associated with a higher risk of 1–5 grade IRP compared with PD-L1 inhibitors.

scholarly journals Combination of Immune Checkpoint Inhibitors and Radiotherapy for Advanced Non-Small-Cell Lung Cancer and Prostate Cancer: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zexi Xu ◽  
Jia Feng ◽  
Yiming Weng ◽  
Yao Jin ◽  
Min Peng
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Fixed Effects ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Clinical Manifestations ◽  
Grade 3

Objectives. Immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) have emerged as a breakthrough therapy in the treatment of various cancers. The combination has a strong rationale, but data on their efficacy and safety are still limited. Hence, we comprehensively searched the database and performed this study to elucidate the clinical manifestations of this combined strategy. Methods. We performed a meta-analysis of randomized trials that compared ICI plus RT with placebo plus RT or ICI alone for the treatment of advanced nonsmall-cell lung cancer (NSCLC) and prostate cancer. The outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events. A fixed-effects or random-effects model was adopted depending on between-study heterogeneity. Results. Three trials involving 1584 patients were included. ICI plus RT was significantly associated with improvement of OS (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.70–0.94, P = 0.004 ), PFS (HR = 0.64; 95% CI 0.56–0.72, P < 0.00001 ), and DCR (relative risk [RR] = 1.38; 95% CI 1.03–1.84, P = 0.03 ). A significant predictor for PFS with the combination of ICI and RT was age, as a significant improvement in PFS (HR = 0.49; 95% CI 0.37–0.64, P < 0.00001 ) was observed in NSCLC patients aged under 65 years. In safety analyses, patients receiving ICI plus RT had a significantly higher incidence of dyspnea (RR = 2.43; 95% CI 1.16–5.08, P = 0.02 ) and pneumonitis of grade 3 or higher (RR = 2.78; 95% CI 1.32–5.85, P = 0.007 ). Conclusion. The combination of ICI and RT was associated with improved OS, PFS, and DCR. Patients under 65 years will be the dominant beneficiaries. However, the incidence of dyspnea and pneumonia of grade 3 or higher also increased, which deserves our vigilance.

A comprehensive meta-analysis of endocrine immune-related adverse events of immune checkpoint inhibitors and outcomes in head and neck cancer and lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14096-e14096 ◽  
Author(s):  
Cristiane Jeyce Gomes-Lima ◽  
John Kwagyan ◽  
Fred King ◽  
Stephen J Fernandez ◽  
Kenneth D Burman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Head And Neck Cancer ◽  
Adverse Events ◽  
Neck Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Grade 3

e14096 Background: Immune checkpoint inhibitors (ICPi) have emerged as an effective treatment for a variety of cancers. However, important immune-related adverse events (irAEs) can occur. The aim of this study was to determine the prevalence of endocrine irAEs in patients with head and neck cancer and lung cancer that have used a ICPi and outcomes. Methods: A systematic literature review was performed within PubMed and EMBASE databases. Search terms included “durvalumab”, “atezolizumab”, “nivolumab”, “pembrolizumab”, “ipilimumab”, “head & neck cancer”, “lung cancer”. Studies published before September 2018 were included. The search was limited to randomized controlled trials (RCTs) phase III written in English. Data were extracted about patient characteristics, interventions, overall survival (OS), progression free survival (PFS), and endocrine irAEs. A summary hazard ratio (HR) and 95% confidence interval were calculated using the software Comprehensive Meta-Analysis and a scatter plot was generated. Results: Twelve RCTs comprising 7060 patients were reviewed; 3815 used an ICPi (treatment arm). The mean follow-up time of 12.2 months ± 7.1 SD. The survival rate of the treatment arm was enhanced (HR, 0.75; 95% CI, 0.70-0.80), compared to the alternate arm. Similarly, the PFS of the treatment arm was improved (HR, 0.77; 95% CI, 0.72-0.81) but with a higher incidence of endocrine irAEs. The most common endocrine irAE reported was hypothyroidism;193 patients in the treatment arm vs. 29 in the alternate arm (p < 0.001); grade 3/4 AE was observed in 10 patients vs. 1 patient, respectively. Other endocrine irAEs were reported in 168 patients in the treatment arm vs. 26 patients in the alternate arm (p < 0.001); grade 3/4 AE was observed in 28 patients vs. 3 patients, respectively. A significant positive correlation between endocrine irAEs and OS was observed (p = 0.019). Conclusions: ICPi are a powerful tool in the treatment of cancer. The prevalence of endocrine irAEs in this meta-analysis was 9%. There is evidence of improved overall survival in patients who developed endocrine irAEs. Further studies are needed to correlate the development of irAEs and OS advantage.

scholarly journals Role of immune-checkpoint inhibitors in lung cancer

2018 ◽  
Vol 12 ◽  
pp. 175346581775007 ◽  
Author(s):  
Prantesh Jain ◽  
Chhavi Jain ◽  
Vamsidhar Velcheti
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Activity

Immune checkpoint inhibitors, mainly drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways, represent a remarkable advance in lung cancer treatment. Immune checkpoint inhibitors targeting PD-1 and PD-L1 are approved for the treatment of patients with non-small-cell lung cancer, with impressive clinical activity and durable responses in some patients. This review will summarize the mechanism of action of these drugs, the clinical development of these agents and the current role of these agents in the management of patients with lung cancer. In addition, the review will discuss the role of predictive biomarkers for optimal patient selection for immunotherapy and management of autoimmune side effects of these agents.

scholarly journals The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer

2019 ◽  
Vol 11 ◽  
pp. 175883591987036 ◽  
Author(s):  
Jia Li Low ◽  
Robert J. Walsh ◽  
Yvonne Ang ◽  
Gloria Chan ◽  
Ross A. Soo
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
First Line

Lung cancer is the most common cancer and leading cause of cancer death. While targeted therapies have redefined treatment options for non-small cell lung carcinoma (NSCLC) with genetic aberrations such as epidermal growth factor and anaplastic lymphoma kinase, many patients do not harbour these oncogenic drivers. Cancer immunology has enabled the development of immune modulators that has dramatically altered the therapeutic landscape of advanced NSCLC. The success of immune-checkpoint inhibitors in pretreated NSCLC has led to the conduct of multiple studies exploring their role in the first-line setting. This article provides an overview of the evolving landscape of immune-checkpoint inhibitors with a focus on the programmed cell-death 1 (PD-1; pembrolizumab, nivolumab) and programmed cell-death ligand 1 (PD-L1; atezolizumab, durvalumab, avelumab) immune-checkpoint inhibitors as single agent or in combination with either chemotherapy or with another immune-checkpoint inhibitor in the treatment of NSCLC, the challenges faced, as well as future perspectives.

scholarly journals Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review

2020 ◽  
Vol 21 (19) ◽  
pp. 7195 ◽  
Author(s):  
Grzegorz Sławiński ◽  
Anna Wrona ◽  
Alicja Dąbrowska-Kugacka ◽  
Grzegorz Raczak ◽  
Ewa Lewicka
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Life Threatening ◽  
Underlying Mechanisms

Lung cancer is a major cause of cancer-related mortality worldwide, both in men and women. The vast majority of patients are diagnosed with non-small-cell lung cancer (NSCLC, 80–85% of lung cancer cases). Therapeutics named immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. They are monoclonal antibodies, and those directed against PD-1 (programmed cell death protein 1) or PD-L1 (programmed cell death-ligand 1) have been used in the treatment of lung cancer and significantly improved the prognosis of NSCLC patients. However, during treatment with ICIs, immune-related adverse events (irAEs) can occur in any organ and any tissue. At the same time, although cardiac irAEs are relatively rare compared to irAEs in other organs, they have a high mortality rate. The two most common clinical manifestations of immunotherapy-related cardiotoxicity are myocarditis and pericarditis. Various types of arrhythmias have been reported in patients treated with ICIs, including the occurrence of life-threatening complete atrioventricular block or ventricular tachyarrhythmias. Here, we aim to summarize the incidence, clinical manifestations, underlying mechanisms, diagnosis, and treatment strategies for ICI-associated cardiotoxicity as these issues become very important in view of the increasing use of ICI in the treatment of lung cancer.

scholarly journals Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Kang Liu ◽  
Zhongke Qin ◽  
Xueqiang Xu ◽  
Ting Li ◽  
Yifei Ge ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Therapy ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Increased Risk ◽  
The Difference ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.MethodsWe carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.ResultsNinety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.ConclusionsAmong ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.Systematic Review RegistrationPROSPERO, identifier CRD42020197039.

284 Real World Data of Sequencing Immune Checkpoint Inhibitors (ICI) after Initial ICI

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A310-A310
Author(s):  
Krishna Gunturu ◽  
Muhammad Awidi ◽  
Rojer Ranjit ◽  
Brendan Connell ◽  
Rachel Carrasquillo ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Clear Understanding ◽  
Real World Data ◽  
World Data

BackgroundICI revolutionized modern Oncology landscape and being utilized in metastatic to adjuvant and neo-adjuvant settings. As Oncologists, we are treating cancer patients with ICI every day, yet there is still a lot that is unknown about these drugs. We don’t have clear understanding of the efficacy and toxicity when sequencing one ICI for another. We conducted a retrospective review of real world data at Lahey Hospital and Medical Center to understand further and to pave path for prospective studies to understand this issue further to improve patient care.MethodsWe retrospectively reviewed Oncology patient charts who received ICI between January1, 2014 to December 18, 2018. Total 483 patients received ICI during this time frame and 22 of these patients received a second ICI either as monotherapy or in combination with other ICI or chemotherapy.ResultsA total of 22 patients received subsequent ICI after the initial ICI as showed in table 1. 15 of the 22 (68%) patients were transitioned from one ICI to another monotherapy. 11 of these patients were transitioned secondary to disease progression (73%), three had immune related adverse events and one was switched per standard of care. One patient had ICI re-challenge. Three patients had a transition from ICI monotherapy to combination ICI therapy. One patient went onto chemo-immunotherapy and 2 patients transitioned from combination ICI to chemo-immunotherapy.Abstract 284 Table 1Real world data of sequencing immune checkpoint inhibitors (ICI) after initial ICIConclusionsICI therapy is evolving and patients are being treated with multiple lines of ICI. In current practices, ICI is frequently being transitioned from cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) classes or combined with chemotherapy or targeted therapy. It would be prudent to explore the effects of sequencing these medications either as a monotherapy or in combination with other therapies to better serve our patients and to prevent financial toxicity.

Sign in / Sign up

Export Citation Format

Share Document