Dataset Information

Indirect comparison of efficacy and safety between immune checkpoint inhibitors and antiangiogenic therapy in advanced non-small-cell lung cancer.

ABSTRACT: In this study, we conducted an indirect comparison analysis to compare the efficacy and safety of immune checkpoint inhibitors with those of antiangiogenic therapy-two effective treatment methods for advanced non-small-cell lung cancer (NSCLC). Eligible randomised control trials of immune checkpoint inhibitors, antiangiogenic therapy, and doublet platinum-based therapy published up to July 2017 were comprehensively analysed. Through the indirect comparison analysis of 37 trials involving 16810 patients, treatments were compared for overall survival (OS) and grade 3-5 adverse events. For first-line treatment, the use of pembrolizumab alone (hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.4-0.91) and a combination of bevacizumab and doublet platinum-based therapy (HR: 0.86; 95% CI: 0.75-0.99) demonstrated substantial survival benefits compared with doublet platinum-based therapy. For subsequent treatment, nivolumab may provide higher efficacy and lower toxicity than antiangiogenic therapy. Overall, anti-PD1 monoclonal antibodies may be superior to antiangiogenic therapy in terms of OS and grade 3-5 adverse events. This meta-analysis suggests that pembrolizumab and nivolumab might be favourable choices for first-line and subsequent treatment, respectively, for patients with advanced NSCLC. Additional randomised control trials are required for a comprehensive evaluation of the outcomes among regimens.

SUBMITTER: Chen JH

PROVIDER: S-EPMC6018789 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Indirect comparison of efficacy and safety between immune checkpoint inhibitors and antiangiogenic therapy in advanced non-small-cell lung cancer.

Chen Jin-Hua JH Yang Jia-Lian JL Chou Che-Yi CY Wang Jiun-Yi JY Hung Chin-Chuan CC

Scientific reports 20180626 1

In this study, we conducted an indirect comparison analysis to compare the efficacy and safety of immune checkpoint inhibitors with those of antiangiogenic therapy-two effective treatment methods for advanced non-small-cell lung cancer (NSCLC). Eligible randomised control trials of immune checkpoint inhibitors, antiangiogenic therapy, and doublet platinum-based therapy published up to July 2017 were comprehensively analysed. Through the indirect comparison analysis of 37 trials involving 16810 p ...[more]

PMID: 29946182

Similar Datasets

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune-related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI-based regimens in patients with advanced lung cancer.MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment-related AEs and irAEs, including grade 1-5 and grade 3-5. The secondary outcomes were grade 1-5 and grade 3-5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node-splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non-small cell lung cancer.ResultsOverall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment-related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1-5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3-5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI-based options provided irAE profiles based on specific organ/system and severity.ConclusionsIn consideration of overall immune-related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI-based treatments for advanced lung cancer. The safety profiles of ICI-based treatments are various by specific irAEs and their severity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42021268650.

Project description:BackgroundIn the first-line treatment of advanced non-small cell lung cancer (NSCLC), for those patients with negative PD-L1 expression, which treatment strategy has the better efficacy and safety between chemotherapy combined with antiangiogenic and with immune checkpoint inhibitors (ICIs) is still unclear due to the absence of head-to-head clinical trials. This study aims to answer the question by performing a systematic review and network meta-analysis (NMA).MethodsElectronic databases (PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov) were systematically searched accordingly to extract eligible studies from inception to October 2022, as well as the abstracts from the most recent main oncology congresses (American Association for Cancer Research (AACR), American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), and European Society for Medical Oncology (ESMO)). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of grades 3 to 5 were independently extracted and collected by two reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We used Cochrane's risk of bias tool for randomized controlled trials through RevMan 5.3 to ascertain the quality of the included studies. NMA with a Bayesian random-effects model was performed by R (version 4.0.4).ResultsAccording to the ranking list from OS-NMA, pembrolizumab combined with chemotherapy has the most effective ranking first (surface under the cumulative ranking (SUCRA) = 0.809844) (pooled HR = 0.65 [0.51-0.83]). On PFS, the triple combination of nivolumab/bevacizumab/chemotherapy ranks first (NMA estimate: HR = 0.35 [0.28-0.43]). On safety, in combination with chemotherapy, sintilimab has minimal toxicity, followed by pembrolizumab+chemo.ConclusionsIn advanced NSCLC patients with negative PD-L1 expression, pembrolizumab+chemo ranks first in the efficacy of OS and does not apparently increase the incidence of any grade ≥ 3 AE as compared with chemo alone. On PFS, pembrolizumab also has advantages, but for patients with squamous cell carcinoma, camrelizumab+chemo seems to be a better choice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021231441.

Project description:BackgroundTherapeutic strategies with immune checkpoint inhibitors (ICIs) counteract the immunosuppressive effects of programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1). ICI treatment has emerged in first- and second-line therapy of non-small cell lung cancer (NSCLC). As immunotherapeutic treatment with ICIs is a dynamic field where new drugs and combinations are constantly evaluated, we conducted an up-to-date systematic review on comparative efficacy and safety in patients with advanced NSCLC.MethodsWe searched PubMed up to February 2020 and Embase, CENTRAL, and clinical trial registries up to August 2018. Additionally, we checked reference lists. We dually screened titles, abstracts and, subsequently, full-texts for eligibility. Two reviewers assessed the risk of bias and graded the certainty of evidence following GRADE (Grading of Recommendations Assessment, Development and Evaluation). For second-line therapy, we performed random-effects meta-analyses. Due to considerable clinical heterogeneity, we reported first-line results narratively.ResultsOf 1497 references, we identified 22 relevant publications of 16 studies. For first-line therapy, a combination of an ICI with chemotherapy improved progression-free survival and overall survival compared to chemotherapy but increased the risk of serious adverse events. Single-agent pembrolizumab increased overall and progression-free survival in patients with PD-L1 expression of ≥50% and resulted in less TRAE than chemotherapy. Compared to placebo, maintenance therapy with durvalumab increased overall and progression-free survival at the downside of higher risk of TRAE. For second-line therapy, a random-effects meta-analysis yielded a statistically significantly improved overall survival (OS) and progression-free survival (PFS) for ICIs compared to docetaxel (HR 0.69; 95% CI: 0.63-0.75 for OS; HR 0.85; 95% CI: 0.77 - 0.93 for PFS; 6 studies, 3478 patients; median OS benefit in months: 2.4 to 4.2). In meta-analysis, risk of any treatment-related adverse events of any grade was lower for ICI than docetaxel as second-line therapy (RR 0.76, 95% CI: 0.73-0.79; 6 studies, 3763 patients).ConclusionIn first-line therapy of patients with advanced NSCLC, ICI is effective when combined with chemotherapy not depending on PD-L1 expression, or as monotherapy in high PD-L1 expressing tumors. For second-line therapy, single-agent ICI improves efficacy and safety compared to docetaxel.

Project description:BackgroundAnlotinib is a new multi-target tyrosine kinase inhibitor (TKI) and has been shown to have antitumor effects and synergistic antitumor effects with immunotherapy only in animal studies and in the 2nd-line treatment in small clinical trials. A real-world study with large sample to compare the efficacy and safety of anlotinib plus immune checkpoint inhibitors (ICIs) with ICIs alone in the multiline treatment of advanced non-small cell lung cancer (NSCLC) was urgently needed.MethodsThe data of 535 advanced NSCLC patients were collected from January 1, 2018, to December 31, 2021. The patients were divided into 2 groups: (I) ICI monotherapy (230 patients); (II) ICI + anlotinib (305 patients). After propensity-score matching (PSM) to reduce the effects of biases and confounding variables, the progression-free survival time (PFS), occurrence of adverse events, disease control rate (DCR), and objective response rate (ORR) of the 2 groups were compared. The effects of clinical factors, including age, gender, gene mutations, tumor proportion score, metastases, and combined radiotherapy, were also analyzed.ResultsAfter PSM, the baseline clinical characteristics were well balanced and the 2 group had a good comparability. Patients in the ICI + anlotinib group had significantly longer median PFS in both the 2nd-line treatment (7.73 vs. 4.70 months; P=0.003) and 3rd-line treatment (5.90 vs. 3.37 months; P=0.020), but the difference lacked statistical significance in the 1st-line treatment (8.40 vs. 5.20 months; P=0.229). The overall median PFS of patients in the ICI + anlotinib group was also much longer than that of patients in the ICI monotherapy group (6.37 vs. 3.90 months; P<0.001). The ICI + anlotinib group also tended to have a higher DCR, a higher ORR, and a higher probability of severe adverse drug reactions during the treatment than the ICI monotherapy group, but the differences were not statistically significant. Combining ICI + anlotinib could improve the outcomes of patients with bone metastasis.ConclusionsAnlotinib + ICI therapy could have greater efficacy in the treatment of advanced NSCLC patients than ICI monotherapy. The probability of adverse events might increase in the combined treatment, but could be controlled.

Dataset Information

Indirect comparison of efficacy and safety between immune checkpoint inhibitors and antiangiogenic therapy in advanced non-small-cell lung cancer.

Publications

Indirect comparison of efficacy and safety between immune checkpoint inhibitors and antiangiogenic therapy in advanced non-small-cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets