scholarly journals Correlation between immune-related adverse events and the efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: systematic review and meta-analysis

2021 ◽  
Author(s):  
Qian Zhang ◽  
Wei Wang ◽  
Qi Yuan ◽  
Li Li ◽  
Yu-Chao Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Low Grade ◽  
Small Cell Lung ◽  
Subgroup Analyses

Abstract Objective Anti-programmed cell death-1 and programmed cell death ligand-1 (PD-1/PD-L1) inhibitors have been proved to have a significant clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Many studies have demonstrated that immune-related adverse events (irAEs) are significantly correlated with clinical efficacy, but the results are not consistent. This meta-analysis aimed to evaluate the associations between irAEs and efficacy. Methods Comprehensive searches were conducted on PubMed and EMBASE database. The HR and 95% CI were used to assess the associations between immune-related adverse events and efficacy of overall survival and progression-free survival. Subgroup analyses were performed based on irAEs type and grade of irAEs. Heterogeneity and publication bias were also assessed by Q test, I2, and funnel plot. Results Compared with non-irAEs, the development of irAEs was significantly improved PFS and OS (PFS: HR = 0.55, 95% CI = 0.51–0.60, p < 0.001; OS: HR = 0.74, 95% CI = 0.68–0.81, p < 0.001). In the subgroup analyses, the occurrence of endocrine irAEs, gastrointestinal irAEs, skin lesions and low-grade irAEs was also significantly correlated with the efficacy. Additionally, the association between severe-grade irAEs and survival benefits on PFS was significant, but not on OS. Conclusions The results indicated that the occurrence of irAEs was significantly associated with a better efficacy in the treatment of NSCLC, especially endocrine, gastrointestinal, skin and low-grade irAEs.

scholarly journals Immune-Related Adverse Events and Their Association With the Effectiveness of PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Real-World Study From China

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoling Chen ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Retrospective Study ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Small Cell ◽  
Small Cell Lung

BackgroundProgrammed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors are increasingly used in China, but no real-world data are available about the immune-related adverse events (irAEs). This real-world retrospective study aimed to assess the safety and effectiveness of PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC) and to analyze the association between irAEs and effectiveness.MethodsThis was a retrospective study of the clinical data of patients with NSCLC treated with PD-1/PD-L1 inhibitors from August 2016 to November 2019 at Beijing Cancer Hospital. The patients were divided into the irAE or non-irAE groups. Overall adverse events, the impact of irAE on tumor response, and the association of irAEs with effectiveness were evaluated.ResultsOne hundred and ninety-one patients were included, including 70 (36.6%) patients in the irAE group and 121 (63.4%) patients in the non-irAE group. AE, grades 3–5 AEs, and irAE occurred in 107 (56.0%), 24 (12.6%), and 70 (36.6%) of the patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were higher in the irAE group compared with the non-irAE group (42.0% vs. 25.8%, P=0.038; 91.9% vs. 70.8%, P=0.002). Multivariable analyses identified that irAE were associated with progression-free survival (HR=0.62, 95%CI: 0.43–0.91; P=0.015), but not with overall survival (HR=0.76, 95%CI: 0.44–1.28; P=0.299).ConclusionIn NSCLC treated with PD-1/PD-L1 inhibitors, patients with irAEs showed improved effectiveness over patients without irAEs. Future studies of anti-PD-1/PD-L1 immunotherapy should explore this association and the underlying biological mechanisms of efficacy.

scholarly journals Immune-related adverse events associated with PD-1/PD-L1 Inhibitors used as first-line treatment for advanced non-small cell lung cancer: a Bayesian network meta-analysis of randomized clinical trials

2021 ◽  
Author(s):  
Jingjing Gu ◽  
Weidong Zhang ◽  
Chunming Bian ◽  
Guanhong Huang
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy

Abstract Background In recent years programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), have opened a new era of advanced non-small cell lung cancer (NSCLC) treatment,while yielding higher rates of immune-related adverse events (irAEs) than platinum-based chemotherapy. This network meta-analysis indirectly compared the incidences of irAEs of PD-1/PD-L1 inhibitor + chemotherapy, PD-1/PD-L1 inhibitor alone, and dual PD-1/PD-L1 inhibitor combinations. Methods We found 12 phase II or III randomized clinical trials (RCTs) including 8,453 patients with NSCLC by searching Pubmed, Embase, and the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov. Summary risk ratios(RRs) and 95% confidence interval were used to compare the rate of irAEs for different ICI-based treatments using pairwise and network meta-analysis with random effects. Results In addition to platinum-based chemotherapy, in terms of dermatologic irAEs, durvalumab had the lowest rate compared to pembrolizumab + platinum, nivolumab, atezolizumab + platinum, nivolumab, pembrolizumab, nivolumab + ipilimumab. In terms of gastrointestinal irAEs, pembrolizumab had the lowest rate compared to nivolumab, nivolumab + ipilimumab, durvalumab, atezolizumab + platinum, and pembrolizumab + platinum. For endocrine irAEs, pembrolizumab + platinum had the lowest rate compared to pembrolizumab, atezolizumab + platinum, durvalumab, nivolumab, and nivolumab + ipilimumab. For pneumonitis, atezolizumab had the lowest rate compared to durvalumab nivolumab, atezolizumab + platinum, pembrolizumab + platinum, and pembrolizumab. For liver irAEs, durvalumab had the lowest rate compared to pembrolizumab, nivolumab, atezolizumab + platinum, pembrolizumab + platinum. Conclusions These findings suggested that, for patients with advanced NSCLC at high risk of irAEs, durvalumab for patients with dermatologic and liver irAEs, pembrolizumab for patients with gastrointestinal irAEs, pembrolizumab + platinum for patients with endocrine irAEs, and atezolizumab for patients with pneumonitis may be the preferred treatment regimens rather than other immune-based therapies.

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Specific Immunotherapy ◽  
Meta Analysis ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

Sign in / Sign up

Export Citation Format

Share Document