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Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer.

ABSTRACT: 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.

SUBMITTER: Yi L

PROVIDER: S-EPMC6086108 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer.

Yi Lilan L Zhang Wei W Zhang Hongman H Shen Jie J Zou Jingwen J Luo Peng P Zhang Jian J

Drug design, development and therapy 20180807

<h4>Background</h4>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.<h4>Materials and methods</h4>Three databases, including PubMed, EMBASE, and the Cochrane Library, were systematically searched for available literature until March 1, 2018. Data on tumor response ra ...[more]

PMID: 30122902

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Project description:BackgroundAdjuvant chemotherapy (ACT) is routinely the recommended treatment for patients with advanced non-small cell lung cancer (NSCLC) but remains a controversial option in stage IB patients. We therefore pooled the current evidence to determine the prognostic impact of ACT in stage IB NSCLC patients in the context of the eighth tumor, node, metastasis (TNM) staging system.MethodsFive electronic databases were searched for eligible studies up to December 2020 without language restrictions. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS). Search results were filtered by a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The risk of bias was assessed independently using a modified set. Stata 16.0 was used for general data analysis and meta-analysis, and subgroup analyses were performed to investigate the source of interstudy heterogeneity.ResultsIn all, 12 eligible studies were identified and 15,678 patients included. Our results demonstrated that ACT was associated with improved OS [n=11; hazard ratio (HR) =0.65; 95% confidence interval (CI): 0.60-0.70; P<0.001; I2=33.4%, P=0.131] and DFS (n=9; HR =0.73; 95% CI: 0.63-0.83; P<0.001; I2=66.7%, P=0.002) in stage IB NSCLC patients. Subgroup analysis by histology indicated that administration of ACT conferred more favorable survival to both stage IB squamous cell carcinoma (n=1; HR =0.56; 95% CI: 0.28-0.84; P<0.001) and adenocarcinoma (n=6; HR =0.59; 95% CI: 0.47-0.71; P<0.001; I2=31.0%, P=0.203). Meanwhile, both platinum-based ACT (n=7; HR =0.62; 95% CI: 0.51-0.74; P<0.001; I2=44.8%, P=0.093) and other regimens (n=2; HR =0.66; 95% CI: 0.61-0.72; P<0.001; I2=0.7%, P=0.316) could benefit patients with stage IB disease.DiscussionACT might provide survival benefits to patients with stage IB NSCLC irrespective of histology or regimens. Patient selection and time trend biases were inevitable due to the limitation of retrospective studies. More prospective studies should be initiated to investigate the optimal ACT regimens in different histologic types in stage IB NSCLC patients.

Project description:Background: Studies have reported that advanced NSCLC benefits from celecoxib combined with systematic treatment. However, the optimal combination with different treatments remains unclear. A meta-analysis was conducted to explore treatment combinations. Methods: We searched the relevant literature via PubMed, EMBASE, the Cochrane Library and PMC. The data for the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse effects were obtained. Subgroup analysis was performed according to the treatment pattern. Statistical analyses were carried out using Review Manager 5.3 software. Results: A total of 18 eligible studies were included, with 1178 advanced NSCLC patients. Subgroup analysis revealed that celecoxib combined with chemotherapy or tyrosine kinase inhibitors (TKIs) significantly increased the ORR, with no significant difference between the two groups. Celecoxib combined with chemotherapy improved OS-6 (OR=0.65, 95% CI 0.59-0.71, P<0.001), while OS-6 was not changed with celecoxib combined with TKIs (OR=0.53, 95% CI 0.31-0.73, P=0.82). Differences were apparent between the chemotherapy and TKIs regarding OS-6 (P=0.0392). Celecoxib combined with chemotherapy significantly prolonged OS-12 (OR=0.39, 95% CI 0.33-0.45, P<0.001). In terms of OS-12, there was no significant improvement when celecoxib was combined with radiotherapy or TKIs. Celecoxib combined with chemotherapy or TKIs significantly improved PFS-6 and PFS-12, with no obvious difference in terms of PFS between the two groups. Additionally, celecoxib combined with chemotherapy or TKI treatment increased the incidence of adverse events, with no significant differences between the two groups. Conclusions: Celecoxib combined with chemotherapy or TKIs improved the ORR, with no significant differences between the two groups. In terms of OS, celecoxib combined with chemotherapy was superior to TKIs or radiotherapy. Accordingly, celecoxib combined with chemotherapy increased hematological toxicity and cardiovascular events.

Project description:BackgroundThe use of standard cytotoxic chemotherapy seems to have reached a "treatment plateau". The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.MethodsAccording to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.ResultsThe research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).ConclusionAdding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.

Project description:BackgroundWhether a combination of chemotherapy and erlotinib is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of chemotherapy plus erlotinib versus chemotherapy alone for treating advanced NSCLC.MethodsEMBASE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies. Our protocol was registered in PROSPERO (CRD42014015015).ResultsNine randomized controlled trials with a total of 3599 patients were included. Compared to chemotherapy alone, chemotherapy plus erlotinib was superior in PFS (HR = 0.76 [95% CI 0.62, 0.92], P = 0.006), and no statistically significant difference was observed in OS (HR = 0.94 [95% CI 0.86, 1.03], P = 0.16). Intercalated erlotinib plus chemotherapy demonstrated improvements in PFS (HR = 0.67 [95% CI 0.50, 0.91], P = 0.009) and OS (HR = 0.82 [95% CI 0.69, 0.98], P = 0.03). Continuous erlotinib plus chemotherapy treatment failed to demonstrate improvements in PFS (HR = 0.91 [95% CI 0.80, 1.04], P = 0.16) and OS (HR = 0.98 [95% CI 0.89, 1.09], P = 0.75). The association of chemotherapy plus erlotinib with improvement in PFS was significant in never smoking patients (HR = 0.46 [95% CI 0.37, 0.56], P<0.00001) but not in smoking patients (HR = 0.70 [95% CI 0.49, 1.00], P = 0.05). Among patients with EGFR mutant tumors, chemotherapy plus erlotinib demonstrated significant improvements in PFS (HR = 0.31 [95% CI 0.17, 0.58], P = 0.0002) and OS (HR = 0.52 [95% CI 0.30, 0.88], P = 0.01). Among patients with EGFR wild-type tumors, no statistically significant difference was observed with respect to PFS (HR = 0.87 [95% CI 0.70, 1.08], P = 0.21) and OS (HR = 0.78 [95% CI 0.59, 1.01], P = 0.06).ConclusionCombination of chemotherapy and erlotinib is a viable treatment option for patients with NSCLC, especially for patients who never smoked and patients with EGFR mutation-positive disease. In addition, intercalated administration is an effective combinatorial strategy.

Project description:Lung cancer is the leading cause of death from malignant tumors in China, and non-small cell lung cancer (NSCLC) accounts for >80% of all types of lung cancer. Novel immunotherapeutic agents targeting programmed death protein-1 (PD-1) and its ligands [programmed death ligands (PD-L)1 and 2] have emerged as important therapeutic measures and trends in the treatment of advanced NSCLC. Sintilimab (trade name, Daboshu) is a humanized IgG4 monoclonal antibody targeting PD-1 that was developed by Innovent Biologics and Eli Lilly and Company. Studies have shown that sintilimab has the characteristics of high affinity, long-lasting stability and an increased target occupancy rate, and that it is a broad-spectrum drug. The present study uses a meta-analysis to evaluate the safety and efficacy of sintilimab in treating advanced NSCLC. The PubMed, Cochrane Library, Embase, Chinese Biomedical Literature, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journal and Wanfang Medical databases were searched from their establishment until October 2021. Randomized controlled trials of patients with NSCLC who were treated with conventional chemotherapy (chemotherapy) plus sintilimab treatment or sintilimab alone, compared with a chemotherapy group, were included, and a meta-analysis was performed using RevMan 5.3 software. The findings revealed that there was no significant difference between the conventional chemotherapy group and the sintilimab group in terms of the overall incidence of adverse drug reactions (ADR) or grade 3-5 ADRs (risk ratio, 1.04; 95% confidence interval, 0.96-1.14; P=0.33), respectively. Sintilimab coupled with chemotherapy outperformed standard chemotherapy in treating advanced NSCLC. The ADRs did not differ considerably from those of conventional chemotherapy, which will help in the assessment of the clinical efficacy of sintilimab combined with chemotherapy and conventional chemotherapy in treating advanced NSCLC.

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: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.

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Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer.

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Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer.

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