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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

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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

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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: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:BackgroundTo the authors' knowledge, race-based differences in efficacy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) have not been studied to date due to the underrepresentation of patients of minority backgrounds in pivotal trials. In the current study, the authors examined real-world differences in outcome in a diverse patient population.MethodsThe authors retrospectively analyzed the clinical outcomes of patients with advanced NSCLC who were treated with single-agent immune checkpoint blockade (ICB) between 2013 and July 2018 at Winship Cancer Institute of Emory University in Atlanta, Georgia. Primary efficacy comparison between Black patients and White patients was performed using bivariate and multivariate analyses for overall survival (OS) and progression-free survival (PFS).ResultsData from 257 patients were analyzed. The median age of the patients was 69 years; 50.6% of the patients were female, 63.4% were White, 29.5% were Black, and 7.1% of the patients were of "other" race. ICB was the first-line treatment in 51 patients (19.9%), the second-line treatment in 161 patients (62.6%), and the third-line treatment in 33 patients (12.9%). The most commonly used agents were nivolumab (49.0%), pembrolizumab (25.2%), and atezolizumab (21.3%). No differences with regard to OS (P = .839) and PFS (P = .235) were noted between Black and White patients. The sample overall response rate was 20.6% (15.2% in Black patients and 23.1% in White patients). No differences with regard to OS (P = .081) and PFS (P = .176) were observed between female and male patients. The rate of immune-related adverse events was found to be similar in Black and White patients (20.0% vs 29.9%; P = .148). On multivariate analysis, race was not found to be significantly associated with OS or PFS.ConclusionsReal-world analysis of the authors' institutional experience demonstrated similar efficacy and tolerability of ICB in Black versus White patients with advanced NSCLC. Larger multi-institutional studies including other US minority populations would make the findings of the current study more generalizable.

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.

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