Efficacy and Safety of Ipilimumab plus Chemotherapy for Advanced Lung Cancer: A Systematic Review and Meta-Analysis

ABSTRACTBackgroundImmune checkpoint inhibitors have brought hope for patients with advanced lung cancer, among which PD-1/PD-L1 and CTLA-4 inhibitors have achieved considerable results. This meta-analysis aims to investigate the efficacy and safety of PD-1/PD-L1 combined with CTLA-4 antibodies in patients with advanced lung cancer.Materials and MethodsRandomized controlled trials (RCTs) study of PD-1/PD-L1 combined with CTLA-4 inhibitors for advanced lung cancer was searched in the database for systematic review and meta-analysis.ResultsThe meta-analysis finally included 4 trials (actually 3 trials), and the results showed that the overall response rate of PD-1/PD-L1 combined with CTLA-4 inhibitor was higher than that of the control group (ORR = 2.29 [95% CI 1.58 3.32], P <0.0001). PFS significantly improved compared with conventional treatment (HR = 0.69 [95% CI 0.56, 0.85], P = 0.0005), which was statistically significant. OS also improved but did not statistically significant (HR = 0.80 [95% CI 0.61, 1.05], P = 0.11). PD-1/PD-L1 combined with CTLA-4 inhibitors had a higher incidence of adverse reactions than conventional treatment (OR = 1.72 [95% CI 0.59, 5.09], P = 0.33), but the incidence of grade≥3 AEs was lower than the control group (OR = 0.96 [95% CI 0.64, 1.44], P = 0.85).ConclusionDouble checkpoint inhibitor PD-1/PD-L1 combined with CTLA-4 antibody has synergistic anti-cancer activity and improved ORR and PFS in lung cancer. Adverse reactions are more common than conventional treatment, but are generally controllable. Therefore, PD-1/PD-L1 combined with CTLA-4 inhibitors provides a beacon for the treatment of advanced lung cancer, which has guiding significance for the treatment selection in the future.

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Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

Current Cancer Drug Targets ◽

10.2174/1568009618666180430124738 ◽

2019 ◽

Vol 19 (3) ◽

pp. 199-209 ◽

Cited By ~ 1

Author(s):

Bing-Di Yan ◽

Xiao-Feng Cong ◽

Sha-Sha Zhao ◽

Meng Ren ◽

Zi-Ling Liu ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Specific Immunotherapy ◽

Meta Analysis ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

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