scholarly journals Comparative Safety of Immune Checkpoint Inhibitors and Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

2021 ◽  
Author(s):  
Ching-Yi Chen ◽  
Chi-Hsien Huang ◽  
Wang-Chun Chen ◽  
Ming-Shyan Huang ◽  
Yu-Feng Wei
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3 ◽  
Nsclc Patients ◽  
Combination Regimens

Abstract Backgrounds: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the standard of care for first-line therapy in metastatic non-small cell lung cancer (NSCLC) patients without actionable mutations. The safety ranking of different ICI and CT combination regimens has not been investigated. This study was aimed to provide a toxicity profile and safety ranking of different ICI and CT combination regimens.Methods: We performed comprehensive searches of phase 2 and 3 randomized clinical trials (RCTs) comparing different ICI regimens (alone or combination) or CT for the first-line treatment of advanced NSCLC. Outcomes of interest were the cumulative incidence of any treatment-related adverse events (TRAEs), grade 3-5 TRAEs (grade 3-5), any immune-related adverse events (irAEs), and grade 3-5 irAEs (grade 3-5). Odds ratios and 95% credible intervals were calculated as summary statistics to quantify the effect of different ICI combination regimens. Results: We included 23 RCTs from 2016 to 2021 with a total of 14,378 patients. The incidence of any TRAEs and grade 3-5 TRAEs ranked from high to low were ICI-CT (probability: 74.88%), ICI-ICI-CT (50.60%), CT alone (74.79%), ICI-ICI (98.37%), and ICI monotherapy (99.37%). Adding CT to ICI regimens resulted in a higher incidence of any grade or grade 3-5 TRAEs compared to ICI-ICI combinations or ICI monotherapy. However, ICI-ICI-CT combinations did not result in a higher incidence of TRAEs than ICI-CT combinations. For any irAEs and grade 3-5 irAEs, the ranking was ICI-ICI (probability: 97.38), ICI monotherapy (96.98%), ICI-CT (99.44%), and CT alone (99.98%). Notably, the incidence of any grade and grade 3-5 irAEs was lower when adding CT to ICI monotherapy. Conclusion: Lack of head-to-head comparisons, these findings provide evidence for clinical decision-making when considering different ICI combination regimens for advanced NSCLC patients.

scholarly journals Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wang ◽  
Zhixuan Ren ◽  
Bentong Yu ◽  
Jian Tang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cancer Genomics ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Introduction Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC Methods In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics. Results 3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients. Conclusion Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.

scholarly journals Pretreatment hemoglobin level as a predictor to evaluate the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592097004
Author(s):  
Zhibo Zhang ◽  
Fan Zhang ◽  
Fang Yuan ◽  
Ye Li ◽  
Junxun Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Cohort Analysis ◽  
Clinicopathological Characteristics ◽  
Small Cell ◽  
Matched Cohort ◽  
Small Cell Lung ◽  
Nsclc Patients

Background: Targeting immune checkpoints represents an immense breakthrough in cancer therapeutics. The prognostic value of hemoglobin (Hb) has been investigated in many malignancies including non-small cell lung cancer (NSCLC). However, the prognostic impact of pretreatment Hb count for immune checkpoint inhibitors (ICIs) in advanced NSCLC patients remains unclear. Methods: A total of 310 late-stage NSCLC patients who received ICI therapies between January 2015 and March 2019 were prospectively enrolled. We used a propensity score-matched cohort analysis for this study. Patients’ clinicopathological characteristics and pretreatment Hb concentration were assessed against the progression-free survival (PFS) and overall survival (OS) using the Kaplan–Meier method and Cox proportional hazards regression. Results: A propensity score (PS)-matched cohort analysis was applied to adjust for potential bias and to create two comparable groups according to patients’ clinicopathological characteristics. The patients with normal baseline Hb levels (⩾110 g/L) had significantly longer PFS [median: 10.0 versus 4.0 months, hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46−0.86; p = 0.001] and OS [median: 17.6 versus 10.5 months, HR (95% CI): 0.56 (0.40−0.79); p < 0.001] than those with decreased Hb count (<110 g/L) in a PS-matched cohort ( n = 255). For patients with normal pretreatment Hb levels, ICI combination therapy was significantly associated with better PFS [median: 11.1 versus 8.0 months, HR (95% CI): 0.74 (0.50−1.06); p = 0.09] and OS [median: 26.0 versus 12.9 months, HR (95% CI): 0.56 (0.37−0.86); p = 0.008] than monotherapy, but there was no such trend for patients with decreased baseline Hb levels. Conclusion: Our findings showed that normal pretreatment Hb count served as a favorable prognostic marker in advanced NSCLC patients treated with ICIs, representing an economical biomarker with readily measuring performance among all reported ones.

scholarly journals Novel Biomarkers of Dynamic Blood PD-L1 Expression for Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiao Yang ◽  
Mingjing Chen ◽  
Jiaoyang Gu ◽  
Kai Niu ◽  
Xianlan Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundImmune checkpoint inhibitors (ICIs) have become a high-profile regimen for malignancy recently. However, only a small subpopulation obtains long-term clinical benefit. How to select optimal patients by reasonable biomarkers remains a hot topic.MethodsPaired tissue samples and blood samples from 51 patients with advanced malignancies were collected for correlation analysis. Dynamic changes in blood PD-L1 (bPD-L1) expression, including PD-L1 mRNA, exosomal PD-L1 (exoPD-L1) protein and soluble PD-L1 (sPD-L1), were detected after 2 months of ICIs treatment in advanced non-small-cell lung cancer (NSCLC) patients. The best cutoff values for progression-free survival (PFS) and overall survival (OS) of all three biomarkers were calculated with R software.ResultsIn 51 cases of various malignancies, those with positive tissue PD-L1 (tPD-L1) had significantly higher PD-L1 mRNA than those with negative tPD-L1. In 40 advanced NSCLC patients, those with a fold change of PD-L1 mRNA ≥ 2.04 had better PFS, OS and best objective response (bOR) rate. In addition, a fold change of exoPD-L1 ≥ 1.86 was also found to be associated with better efficacy and OS in a cohort of 21 advanced NSCLC cases. The dynamic change of sPD-L1 was not associated with efficacy and OS. Furthermore, the combination of PD-L1 mRNA and exoPD-L1 could screen better patients for potential benefit from ICIs treatment.ConclusionThere was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients.

scholarly journals The role of ERBB4 mutations in the prognosis of advanced non-small cell lung cancer treated with immune checkpoint inhibitors

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Xilin Hu ◽  
Hanlin Xu ◽  
Qianwen Xue ◽  
Ruran Wen ◽  
Wenjie Jiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cancer Genomics ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Immune checkpoint inhibitors (ICIs) have witnessed the achievements of convincing clinical benefits that feature the significantly prolonged overall survival (OS) of patients suffering from advanced non-small cell lung cancer (NSCLC), according to reports recently. Sensitivity to immunotherapy is related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, a further investigation into the novel biomarkers of the prognosis on ICIs treatment is required. In addition, there is an urgent demand for the establishment of a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients. Methods In this study, the gene mutation and clinical data of NSCLC patients was obtained from the TCGA database, followed by the analysis of the detailed clinical information and mutational data relating to two advanced NSCLC cohorts receiving the ICIs treatment from the cBioPortal of Cancer Genomics. The Kaplan–Meier plot method was used to perform survival analyses, while selected variables were adopted to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from the cBioPortal of Cancer Genomics. Results The mutation frequencies of TP53 and ERBB4 were 54% and 8% in NSCLC, respectively. The mutual exclusive analysis in cBioPortal has indicated that ERBB4 does show co-occurencing mutations with TP53. Patients with ERBB4 mutations were confirmed to have better prognosis for ICIs treatment, compared to those seeing ERBB4 wild type (PFS: exact p = 0.017; OS: exact p < 0.01) and only TP53 mutations (OS: p = 0.021). The mutation status of ERBB4 and TP53 was tightly linked to DCB of ICIs treatment, PD-L1 expression, TMB value, and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy. Conclusion ERBB4 mutations could serve as a predictive biomarker for the prognosis of ICIs treatment. The systematic nomogram was proven to have the great potential for evaluating the efficacy of ICIs therapy for advanced NSCLC patients.

scholarly journals The Role of ERBB4 Mutations in the Prognosis of Advanced Non-small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Xilin Hu ◽  
Ruran Wen ◽  
Hanlin Xu ◽  
Wenjie Jiao ◽  
Kaihua Tian
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cancer Genomics ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Introduction: Recently, immune checkpoint inhibitors (ICIs) has been reported to achieved convincing clinical benefits and significantly prolonged the overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients. Sensitivity to immunotherapy was related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, novel biomarkers for the prognosis to ICIs treatment need to be further investigated, and it is an urgent demand to establish a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients.Methods: In this study, gene mutation and clinical data of NSCLC patients was obtained from the TCGA database. Then, we analyzed the detailed clinical information and mutational data of two advanced NSCLC cohorts received ICIs treatment from the cBioPortal for Cancer Genomics. The Kaplan-Meier plot method was used to perform survival analyses, selected variables were used to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from cBioPortal for Cancer Genomics.Results: Mutation frequencies of TP53 and ERBB4 was 54% and 8% in NSCLC, respectively. Mutual exclusive analysis in cBioPortal indicated that ERBB4 does show co-occurencing mutations with TP53. Patients harbored ERBB4 mutations were confirmed to have a better prognosis for ICIs treatment, compared to ERBB4 wild type (PFS: p=0.0360; OS: p=0.0378) and only TP53 mutations (OS: p=0.021). The mutation status of ERBB4 and TP53 are tightly linked to DCB for ICIs treatment, PD-L1 expression, TMB value and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy.Conclusion: ERBB4 mutations could serve as a predicting biomarker for prognosis of ICIs treatment. The systematic nomogram was proven to have a great potential to evaluate the efficacy of ICIs therapy for advanced NSCLC patients.

scholarly journals Association Between Efficacy of Immune Checkpoint Inhibitors and Sex: An Updated Meta-Analysis on 21 Trials and 12,675 Non-Small Cell Lung Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Chongxiang Xue ◽  
Shuyue Zheng ◽  
Huijing Dong ◽  
Xingyu Lu ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundMounting randomized clinical trials have proved that immune checkpoint inhibitors (ICIs) achieved better overall survival (OS) and progression-free survival (PFS) than chemotherapy drugs for advanced non-small cell lung cancer (NSCLC) patients. However, some literatures have indicated that different sexes might not have equal immune response. Also, no agreement reached on the issue whether therapeutic benefit of ICIs is related to sex.ObjectivesTo explore the association between efficacy of ICIs for NSCLC patients and their sexes and summarize overall treatment-related adverse events (TRAEs) in an exploratory manner.MethodsWe performed this systematic review and meta-analysis of all potentially relevant studies retrieved from PubMed, EMBASE, and the Cochrane Library until June 2021, for eligible randomized controlled trials (RCTs) comparing immunotherapy with chemotherapy in advanced NSCLC patients. Literature screening, summary data extraction was performed independently and in duplicate. The pooled hazard ratio (HR) and 95% confidence interval (CI) of OS, PFS and TRAEs were calculated, applying STATA software and random-effects models. This study was registered in international prospective register of systematic reviews (PROSPERO), number CRD42020210797.ResultsTwenty-one trials involving 12,675 NSCLC patients were included. For patients with advanced NSCLC, ICIs significantly prolonged the OS (males: HR 0.73, 95%CI 0.67-0.79; females: HR 0.73, 95%CI 0.61-0.85) and PFS (males: HR 0.62, 95%CI 0.55-0.70; females: HR 0.68, 95%CI 0.55-0.81) versus chemotherapy. Overall, there was no statistical difference between their sexes (OS: P = 0.97; PFS: P = 0.43), respectively. Owing to insufficient TRAEs data of different sexes, we only found immunotherapy for NSCLC patients had more all-grades (RR 0.88; 95%CI 0.82-0.95) and 3-5 grades (RR 0.60; 95%CI 0.47-0.75) AEs compared with chemotherapy.ConclusionOur findings indicated that the interaction between immunotherapy efficacy and different sexes was equally evident. Overall, patients with NSCLC could obtain more benefits from ICIs than chemotherapy regimen regardless of their sexes.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020210797.

Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A real-world perspective.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21213-e21213
Author(s):  
Saleha Rizwan ◽  
Khaled Alhamad ◽  
Stephen Abel ◽  
Veli Bakalov ◽  
Robin Raquel Rodriguez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Small Cell ◽  
Insurance Status ◽  
Small Cell Lung ◽  
Ecog Performance Status ◽  
Nsclc Patients

e21213 Background: Lung cancer is the leading cause of death in males and females in the United States. Approximately 85% of all cases are classified as non-small cell lung cancer (NSCLC) with majority diagnosed at an advanced stage. Unfortunately, response to traditional chemotherapy (ChT) has been poor with a five-year survival rate of 6% in metastatic NSCLC. Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape for advanced NSCLC and are being utilized alone or in combination with ChT as the standard first-line therapy. With widespread use of ICIs, immune-related adverse events (irAE) are commonly seen and in some studies their occurrence correlates with improved outcomes. The aim of our study was to evaluate whether development of irAEs has an impact on survival in NSCLC. Methods: We performed a retrospective analysis on stage IV NSCLC patients treated with ChT, ChT plus ICI, or ICI monotherapy from December 2016 to December 2019. Univariable and multivariable analyses identified characteristics predictive of progression-free survival (PFS) and overall survival (OS). OS was calculated using Kaplan Meier curves. Log-rank statistics were used to assess statistical significance between groups. Multivariable logistic regression was performed to identify predictors of survival. Results: 193 patients were evaluated out of which 92 (47.2%) received ChT plus pembrolizumab, 69 (35.4%) received pembrolizumab alone and 32 (16.4%) received ChT alone. 130 patients were found to have no irAEs compared to 57 patients who were noted to have any grade of irAE. The median PFS was 17.4 months (irAE group) vs. 8.5 months (non-irAE group) with hazard ratio (HR) of 0.58 (95% CI: 0.41 to 0.80, p = 0.001). The median OS was 29.4 months (irAE group) vs. 14.4 months (non-irAE group) with HR of 0.56 (95% CI: 0.39 to 0.82, p = 0.0026). A multivariate analysis was performed for age, gender, ECOG performance status, insurance status, BMI, PDL1 status and smoking history, amongst other variables. Worse survival outcomes were noted with an ECOG performance status ≥ 2, no history of smoking, and involvement of palliative care. Multivariable logistic regression analysis showed that PDL-1 expression > 50% was the only predictor of developing an irAE. Of note, receipt of ChT in combination with pembrolizumab compared to pembrolizumab alone did not predict for development of irAE. Conclusions: Development of irAEs was associated with doubling of PFS and OS, regardless of whether the ICI was administered alone or in combination with ChT. The differences were statistically significant regardless of age, gender, race, BMI, insurance status or performance status. Our study highlights the correlation between development of irAEs and improved survival outcomes in advanced NSCLC patients treated with ICIs.

scholarly journals Plasma Biomarkers Screening by Multiplex ELISA Assay in Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 97
Author(s):  
Adrien Costantini ◽  
Paul Takam Kamga ◽  
Catherine Julie ◽  
Alexandre Corjon ◽  
Coraline Dumenil ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Elisa Assay ◽  
Small Cell Lung ◽  
Plasma Biomarkers

Immune checkpoint inhibitors (ICIs) are commonly used in patients with advanced non-small cell lung cancer (NSCLC). An unmet need remains for new biomarkers associated with ICIs. In this study, consecutive patients with advanced NSCLC treated with nivolumab or pembrolizumab were included. Plasma at ICIs initiation was prospectively collected and a multiplex ELISA assay testing 48 cytokines and growth factors was performed. Exploratory endpoints were the association between plasma biomarkers with outcome and grade III–IV immune related adverse events (irAEs). Thirty-five patients were included. Patients without clinical benefit (n = 22) had higher pre-ICI soluble Hepatocyte Growth Factor (sHGF) (210.9 vs. 155.8 pg/mL, p = 0.010), lower pre-ICI soluble Fibroblast Growth Factor (sFGF) (4.0 vs. 4.8 pg/mL, p = 0.043) and lower pre-ICI interleukine-12 (IL-12) (1.3 vs. 2.2 pg/mL, p = 0.043) concentrations. Patients with early progression (n = 23) had higher pre-ICIs sHGF (206.2 vs. 155.8 pg/mL, p = 0.025) concentrations. Patients with low sHGF levels at ICIs initiation had longer progression-free survival and overall survival than those with high sHGF levels: respectively 2.5 vs. 8.0 months (p = 0.002), and 5.5 vs. 35.0 months (p = 0.001). TNF-α, IL-16, IL-12p40 and MCP3 were associated with high grade irAEs. This study shows the potential association between several plasma biomarkers with outcome and grade 3–4 IrAEs in advanced NSCLC treated with ICIs.

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