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Anlotinib for refractory advanced non-small-cell lung cancer: A systematic review and meta-analysis.

ABSTRACT: OBJECTIVE:To assess the efficacy and toxicity of anlotinib for the treatment of refractory advanced non-small-cell lung cancer (NSCLC). METHODS:We systematically searched databases for randomized controlled trials on anlotinib treatment for patients with advanced NSCLC published until November 6, 2020. Articles were assessed and data were extracted independently by two investigators. Further, we analyzed hazard ratios (HRs) for progression-free and overall survival (PFS and OS, respectively). In addition, we analyzed risk ratio (RR) for overall response and disease control rates (ORR and DCR, respectively) and the odds ratio (OR) for the main adverse events (AEs) using RevMan 5.3 software. RESULTS:This analysis included 594 patients from three clinical studies. The pooled HRs for PFS and OS were 0.27 (95% confidence interval (CI): 0.22-0.33, P < 0.001) and 0.68 (95% CI: 0.56-0.83, P < 0.001), respectively, indicating that anlotinib administration significantly improved PFS and OS in patients with advanced NSCLC. The pooled RRs for ORR and DCR were 11.62 (95% CI: 2.75-49.14, P < 0.001) and 2.30 (95% CI: 1.91-2.77, P < 0.001), respectively, indicating that anlotinib administration in patients with advanced NSCLC improved ORR and DCR. The pooled OR for AEs of grade 3 or higher was 2.94 (95% CI: 1.99-4.35, P < 0.001), indicating that AEs of grade 3 or higher were more prevalent in the anlotinib group than in the placebo group. CONCLUSION:Anlotinib, an effective choice of third- or later line therapy for patients with refractory advanced NSCLC, provides clinical benefits in terms of PFS, OS, ORR, and DCR. AEs associated with anlotinib were tolerable.

SUBMITTER: Yu G

PROVIDER: S-EPMC7703897 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Anlotinib for refractory advanced non-small-cell lung cancer: A systematic review and meta-analysis.

Yu Guocan G Shen Yanqin Y Xu Xudong X Zhong Fangming F

PloS one 20201130 11

<h4>Objective</h4>To assess the efficacy and toxicity of anlotinib for the treatment of refractory advanced non-small-cell lung cancer (NSCLC).<h4>Methods</h4>We systematically searched databases for randomized controlled trials on anlotinib treatment for patients with advanced NSCLC published until November 6, 2020. Articles were assessed and data were extracted independently by two investigators. Further, we analyzed hazard ratios (HRs) for progression-free and overall survival (PFS and OS, re ...[more]

PMID: 33253313

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Project description:Currently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator. Electronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes. A total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer. Altogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.

Project description:Background:The prognostic value of Metformin for concurrent non-small cell lung cancer (NSCLC) has been controversial in previous individual studies and meta-analyses. In order to further investigate the value of this medication, we conducted a systematic review and meta-analysis for patients with advanced or inoperable NSCLC. Methods:We searched articles from PubMed, Scopus and Web of Science databases; the time interval was from the inception date of the databases to 1 September 2017. Inclusion criteria for eligible studies were: advanced or inoperable NSCLC; Metformin as an experimental group, and non-Metformin usage as a control group; progression-free survival (PFS) or overall survival (OS) as the outcome, with available hazard ratio (HR). Data synthesis was conducted based on the random-effect model. Results:From a total of 97 articles in databases, we included seven eligible studies. Among them, only one study compared Metformin usage and non-Metformin usage for NSCLC patients who didn't have diabetes mellitus (DM): no significant difference was found in either OS or PFS. The remaining six studies compared Metformin usage and non-Metformin usage for patients with concurrent NSCLC and DM: according to meta-analysis, significantly prolonged OS was found in Metformin usage rather than non-Metformin usage [pooled HR =0.87 (0.77-0.99), P=0.04]; no significant difference was indicated in PFS [pooled HR =0.85 (0.67-1.07), P=0.16]. In subgroup analysis, among patients with late-stage NSCLC and DM, significant difference was found, regardless of OS [pooled HR =0.81 (0.70-0.94), P<0.01] or PFS [pooled HR =0.71 (0.58-0.88), P<0.01]. However, among patients with local advanced NSCLC and DM, there was no significant difference [OS: pooled HR =1.05 (0.79-1.40), P=0.74; PFS: pooled HR =0.94 (0.68-1.32), P=0.74]. Conclusions:The prognostic value of Metformin for concurrent late-stage NSCLC and DM was demonstrated. It deserves further confirmation and explanation.

Project description:Background:The clinical benefit of a selective cyclooxygenase-2 inhibitor, celecoxib, combined with anticancer therapy in advanced non-small-cell lung cancer (NSCLC) remains unclear. A meta-analysis was performed to address the efficacy and safety of celecoxib in patients with advanced NSCLC. Materials and methods:Three databases, including PubMed, EMBASE, and the Cochrane Library, were systematically searched for available literature until March 1, 2018. Data on tumor response rates, one-year survival, overall survival, progression-free survival, and toxicities were extracted from the included randomized clinical trials. Subgroup analysis was carried out according to the line of treatment. Review Manager 5.3 software was applied to conduct the meta-analysis. Results:A total of 7 randomized controlled trials involving 1,559 patients with advanced NSCLC were enrolled for analysis. The pooled overall response rate (ORR) of celecoxib added to systemic therapy was not significantly improved (risk ratio [RR] =1.14, 95% CI =0.96-1.35, P=0.13). Additionally, no differences were observed between the celecoxib and placebo groups regarding 1-year survival (RR =0.99, 95% CI =0.88-1.12, P=0.91). Subgroup analysis showed that adding celecoxib to the first-line treatment significantly improved the ORR (RR =1.21, 95% CI =1.01-1.44, P=0.04) and partial response rate (RR =1.26, 95% CI =1.01-1.58, P=0.04). The aggregated Kaplan-Meier analysis found no significant difference between celecoxib and placebo regarding the 5-year overall survival (median, 12.9 vs 12.5 months, P=0.553) and 5-year progression-free survival (median, 7.4 vs 7.2 months, P=0.641). The increased RR of leukopenia (RR =1.25, 95% CI =1.03-1.50) and thrombocytopenia (RR =1.39, 95% CI =1.11-1.75) indicated that celecoxib increased hematologic toxicities (grade ?III). However, celecoxib did not increase the related risks of thrombosis or embolism (RR =1.26, 95% CI =0.66-2.39) and cardiac ischemia (RR =1.16, 95% CI =0.39-3.44). Conclusion:Celecoxib had no benefit on survival indices for advanced NSCLC but improved the ORR of first-line treatment. Additionally, celecoxib increased the rate of hematologic toxicities without increasing the risk of cardiovascular events.

Project description:Anlotinib is a small-molecule RTK inhibitor that has achieved certain results in further-line treatment, but many patients do not respond to this drug and lack effective methods for identification. Although radiomics has been widely used in lung cancer, very few studies have been conducted in the field of antiangiogenic drugs. This study aims to develop a new model to predict the efficacy of patients receiving anlotinib by combining pretreatment computed tomography (CT) radiomic characters with clinical characters, in order to assist precision medicine of pulmonary cancer. 254 patients from seven institutions were involved in the study. Lesions were selected according to the RECIST 1.1 criteria, and the corresponding radiomic features were obtained. We constructed prediction models based on clinical, NCE-CT, and CE-CT radiomic features, respectively, and evaluated the prediction performance of the models for training sets, internal validation sets, and external validation sets. In the RAD score only model, the area under curve(AUC) of the NCE-CT cohort was 0.740 (95% CI: 0.622, 0.857) for the training set, 0.711 (95% CI: 0.480, 0.942) for the internal validation set, and 0.633(95% CI: 0.479, 0.787) for the external validation set, while that of the CE-CT cohort was 0.815 (95% CI: 0.705, 0.926) for the training set, 0.771 (95% CI: 0.539, 1.000) for the internal validation set, and 0.701 (95% CI: 0.489, 0.913) for the external validation set. In the RAD score-combined model, the AUC of the NCE-CT cohort was 0.796 (95% CI: 0.691, 0.901) for the training set, 0.579 (95% CI: 0.309, 0.848) for the internal validation set, and 0.590 (95% CI: 0.427, 0.753) for the external validation set, while that of the CE-CT cohort was 0.902 (95% CI: 0.828, 0.977) for the training set, 0.865 (95% CI: 0.696, 1.000) for the internal validation set, and 0.837 (95% CI: 0.682, 0.992) for the external validation set. In conclusion, radiomics has accurate predictions for the efficacy of anlotinib. CE-CT-based radiomic models have the best predictive potential in predicting the efficacy of anlotinib, and model predictions become better when they are combined with clinical characteristics.

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Dataset Information

Anlotinib for refractory advanced non-small-cell lung cancer: A systematic review and meta-analysis.

Publications

Anlotinib for refractory advanced non-small-cell lung cancer: A systematic review and meta-analysis.

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