scholarly journals The efficacy and safety of immune checkpoints inhibitors plus radiotherapy as a combination therapy for advanced non-small cell lung carcinoma: a meta-analysis

2020 ◽  
Author(s):  
Dan Yang ◽  
DaiRong Li ◽  
LuLu Wang ◽  
LuMi Huang ◽  
JianLin Long ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Radiotherapy Group

Abstract BackgroundImmune checkpoint inhibitors have showed good efficacy in advanced non-small-cell lung cancer(NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of immune checkpoint inhibitors combined with radiotherapy for patients with advanced NSCLC.MethodsWe used many proper keywords to perform a systematic search in databases and performed a meta-analysis of trials that conducted immune checkpoint inhibitors plus radiotherapy as a treatment for advanced non-small-cell lung cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.ResultsTen trials were finally included in this meta-analysis. The combined ORR and DCR was 34% (19%-49%) and 72% (65%-79%). The combined six-month progression-free survival rates (PFSR6m) and one-year overall survival rate(OSR1y) were 50.0% (29.4%-72.8%) and 59.0% (48%-69%). Immune checkpoint inhibitors plus radiotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.64; 95% CI 0.46–0.90; P = 0.01), OS (HR, 0.62; 95% CI 0.46–0.85; P = 0.003). In subgroup analyses, the combined ORR was 31.5% (16.4%-46.6%), combined DCR was 72.1% (63.3%-80.9%), combined PFS6m was 50.0% (20.6%-79.5%) and combined OSR1y was 59.7% (48.1%-71.2%) for anti-PD-1/PD-L1 antibody plus radiotherapy. The combined ORR was 19.5% (9.1%-29.8%) for anti-CTLA4 antibody plus radiotherapy. The combined PFS6m and OSR1y were 58.9% (26.2%-91.7%) and 59.7% (29.7%-89.8%) respectively for the concurrent therapy group. And the combined PFS6m and OS1y were 55.2% (41.6%-68.8%) and 55.7% (42.1%-69.3%) for sequential therapy. For the low-dose radiotherapy group. The combined PFS6m and OS1y were 45.9% (27.0%-64.8%) and 51.6% (37.5%-65.6%). The combined PFS6m and OS1y were 71.1% (37.9%-104.4%) and 67.4% (29.2%-105.6%) separately for high-dose radiotherapy group. When using as first-line therapy. The combined ORR was 53.8% (23.6%-84.1%) and combined ORR was 76.5% (65.0%-88.1%). While as subsequent therapy, the combined ORR and DCR were 25.9% (14.7%-37.2%) and 69.9% (60.9%-78.9%). The combined PFS6m and OS1y were 51.1% (40.3%-61.9%) and 51.8% (40.9%-62.7%).ConclusionsImmune checkpoint inhibitors plus radiotherapy might be an effective and tolerable option as a treatment for advanced NSCLC.

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.

scholarly journals Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2352
Author(s):  
Francesco Fiorica ◽  
Umberto Tebano ◽  
Milena Gabbani ◽  
Mariasole Perrone ◽  
Sonia Missiroli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Metastatic Nsclc ◽  
Nsclc Patients

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.

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.

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.

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