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The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis.

ABSTRACT: The value of immune checkpoint inhibitor (ICI) combination therapy for patients with lung cancer remains unclear. We conducted a meta-analysis using PubMed, Embase, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs) that might provide a reference for clinical practice. The selection criteria were defined according to the population, intervention, comparison, outcome and study design (PICOS) framework. In all, 12 RCTs with 5,989 patients were included in this meta-analysis. Our results showed that ICI combination therapy was significantly associated with the improvement of overall response rate (ORR) (RR =1.44 [95% CI 1.19, 1.74], P=0.0002), progression-free survival (PFS) (HR =0.67 [95% CI 0.59, 0.77], P<0.00001), and OS (HR =0.81 [95% CI 0.70, 0.95], P=0.008) in lung cancer. In subgroup analyses, combination ICI therapy significantly prolonged OS in non-small-cell lung cancer (NSCLC) patients (HR =0.80 [95% CI 0.73, 0.88], P<0.00001) but not in SCLC (HR =0.94 [95% CI 0.82, 1.08], P=0.40) patients. Data suggested that PD-1 inhibitors had higher efficacy and safety profiles than PD-L1 and CTLA-4 inhibitors in combination ICI therapy for lung cancer patients. Furthermore, tolerability analysis revealed higher incidences of grade ?3 AEs, fatigue, and increased transaminases from combination ICI therapy. In conclusion, our meta-analysis indicated that combination ICI therapy should be considered in clinical practice and future study designs for NSCLC patients. However, the current data do not support the large-scale clinical application of combination ICI therapy in SCLC patients.

SUBMITTER: Peng M

PROVIDER: S-EPMC6204847 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis.

Peng Min M Li Xing X Lei Gu G Weng Yi Ming YM Hu Meng Xue MX Song Qi Bin QB

OncoTargets and therapy 20181024

The value of immune checkpoint inhibitor (ICI) combination therapy for patients with lung cancer remains unclear. We conducted a meta-analysis using PubMed, Embase, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs) that might provide a reference for clinical practice. The selection criteria were defined according to the population, intervention, comparison, outcome and study design (PICOS) framework. In all, 12 RCTs with 5,989 patients were included in thi ...[more]

PMID: 30425525

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Project description:Background: Despite the acknowledged benefits of immune checkpoint inhibitor (ICI)-based combination therapy (either with other checkpoint inhibitors, chemotherapy, targeted therapy, or radiotherapy), little is known about the impact of age on the efficacy of ICI -based combination therapy in non-small-cell lung cancer (NSCLC) patients. We conducted a systematic review and meta-analysis to investigate the differences in the benefits of ICI-based combination therapy for NSCLC by age (cut-off age, 65 years). Methods: We systematically searched randomized controlled trials (RCTs) of ICI plus other therapies including other ICIs, chemotherapies, targeted therapies, or radiotherapies, in the PubMed, Embase, and Cochrane databases with available hazard ratios (HRs) and 95% confidence intervals (CIs) for death and disease progression according to patient age. The search deadline was May 25, 2020. First, we calculated the pooled HRs of younger and older patients based on the HRs from each trial. Second, we assessed the pooled ratio of HRs reported in older patients to the HRs reported in younger patients for progression or death by the random-effects model. An estimated pooled HR ratio was lower than 1 indicating a better effect in older patients and higher than 1 indicating a better effect in younger patients. Results: A total of 10 eligible RCTs were included in our meta-analysis. The pooled HR for overall survival (OS) comparing ICI combined with other therapies to non-ICI regimens was 0.67 (95%CI 0.58-0.78) for younger patients and 0.79 (95%CI 0.70-0.90) for older patients. The pooled HRs ratio for OS reported in older patients compared to younger patients was 1.16 (95%CI 0.99-1.34), indicating no statistically significant difference between younger and older patients. Consistent with the findings related to OS, the analysis also demonstrated that ICI-based immunotherapy could significantly prolong progression-free survival (PFS) in younger and older patients (HR = 0.55; 95% CI 0.47-0.66, and HR = 0.64; 95% CI 0.57-0.71). The same results could also be observed in the pooled HRs ratio for PFS (HR = 1.15, 95%CI 0.91-1.46) indicating comparable efficacy of ICI-based combination therapy in younger and older patients with NSCLC. Conclusion: ICI-based combination therapy vs. non-ICI treatment had comparable efficacy in younger and older NSCLC patients with a cut-off age of 65 years.

Project description:Background Although immune checkpoint inhibitors (ICIs) combined with vascular endothelial growth factor receptor (VEGFR)-targeted therapy and sunitinib monotherapy have been widely applied to metastatic renal cell carcinoma (mRCC), effectiveness and safety data are still lacking. To optimize clinical decision-making, we conducted a systematic review and meta-analysis of published randomized clinical trials to characterize the efficacy and the risk of adverse events (AEs) in patients treated with ICIs plus anti-VEGF therapy. Materials and Methods We used PubMed, EMBASE, and the Cochrane Library to retrieve randomized controlled trials (RCTs) published before March 27, 2021. The efficacy outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The pooled risk ratio (RR) and 95% confidence intervals (CI) of AEs were calculated in the safety analysis. Results Six RCTs involving 4,227 patients were identified after a systematic search. For OS, ICI and anti-VEGF combination therapy decreased mortality approximately 30% in the intention-to-treat population (ITT) (hazard ratio (HR) = 0.70, 95% CI: 0.57–0.87), but there was no statistical difference in patients evaluated as “favorable” by the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) criteria compared with monotherapy (HR = 0.90, 95% CI: 0.55–1.46, p = 0.66). In terms of PFS, the progression risk for all participants declined 35% (HR = 0.65, 95% CI: 0.50–0.83) and patients evaluated as “poor” by IMDC benefited further (HR = 0.46, 95% CI: 0.36–0.58). No evident divergence was found in age and sex subgroups. The RRs of all-grade hypertension, arthralgia, rash, proteinuria, high-grade (grades 3–5) arthralgia, and proteinuria developed after combination therapy were increased compared with sunitinib. The risk of high-grade hypertension and rash showed no statistical difference. However, the risk of hand-foot skin reaction (HFSR), stomatitis, and dysgeusia decreased in combination therapy groups. Conclusions Compared with sunitinib, OS, PFS, and ORR were significantly improved in patients receiving ICI and anti-VEGF combination therapy at the expense of increased specific AEs. More attention should be paid to individualized application of these combination therapies to achieve the best benefit-risk ratio in the clinic. Systematic Review Registration [https://inplasy.com/] INPLASY: 202130104.

Project description:BackgroundThe advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.MethodsWe identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.ResultsOverall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.ConclusionICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

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The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis.

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The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis.

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