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Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a systematic review and meta-analysis.

ABSTRACT: Although adoptive immunotherapy (AIT) is a novel emerging target treatment for non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of Science for relevant parallel randomized controlled trials (RCTs) and high-quality observation studies of AIT without any language restrictions. Two investigators reviewed all the texts and extracted information regarding overall survival rate (OS), progression-free survival rate (PFS), objective response rate (ORR), and disease control rate (DCR) from eligible studies; sensitivity analyses and subgroup analyses were also conducted to reduce heterogeneity Of 319 suitable studies, 15 studies (13 RCTs and 2 observation studies) involving 1684 patients were finally included. Compared to the Control therapy (CT) group, the AIT group exhibited better 1-year OS (P = 0.001), 2-year OS (P < 0.001), 3-year OS (P < 0.001), 5-year OS (P = 0.032), 1-year PFS (P < 0.001), and 2-year PFS (P = 0.029). The difference in the ORR (P = 0.293) and DCR (P = 0.123) was not significant between the groups. The subgroup analysis showed that DC/CIK did more benefit to NSCLC patients than LAK and the cycles not associated with AIT efficacy. AIT can significantly improve the OS and PFS with acceptable toxicity for NSCLC. Nevertheless, further multicenter studies are needed to confirm our conclusion and determine which adoptive immunotherapy is associated with the greatest efficacy.

SUBMITTER: Zhao B

PROVIDER: S-EPMC5762575 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a systematic review and meta-analysis.

Zhao Binghao B Zhang Wenxiong W Yu Dongliang D Xu Jianjun J Wei Yiping Y

Oncotarget 20170719 68

Although adoptive immunotherapy (AIT) is a novel emerging target treatment for non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of Science for relevant parallel randomized controlled trials (RCTs) and high-quality observation studies of AIT without any language restrictions. Two investigators reviewed all the te ...[more]

PMID: 29348890

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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:ImportanceRandomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.ObjectiveTo assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.Data sourcesFull-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.Study selectionPhase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.Data extraction and synthesisData extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.Main outcomes and measuresTwo-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.ResultsEight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).Conclusions and relevanceIn this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.

Project description:IntroductionCytokine-induced killer cells (CIK cells) are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment.MethodsWe combined recombinant human endostatin (rh-endostatin) and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells.ResultsOur results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments.ConclusionsOur results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells therapy against lung carcinomas and unmask the mechanisms of the synergistic antitumor efficacy, providing a new rationale for combining antiangiogenesis therapy with immunotherapy in the treatment of lung cancer.

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: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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Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a systematic review and meta-analysis.

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Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a systematic review and meta-analysis.

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