ABSTRACT
Background: Protein-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD-1/PD-L1 combined with anti-angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD-1/PD-L1 combined with AAs as the treatment for patients with advanced NSCLC. Materials and Methods: We comprehensively searched EMBASE, PubMed, Web of Science, CNKI, VIP, and Wanfang databases from January 2017 to September 2022. The Cochrane risk bias tool evaluated the quality of included randomized clinical trials. Newcastle-Ottawa-Scale score was used to evaluate the quality of retrospective studies. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Results: Seventeen articles were finally selected, involving 5182 patients. Meta-analysis results showed that PD1/PD-L1 combined with AAs therapy significantly improved progression-free survival (PFS) (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.50-0.75, P < 0.00001), overall survival (OS) (HR = 0.79, 95% CI: 0.71-0.88, P < 0.00001), and objective response rate (ORR) (risk ratio = 0.88, 95% CI: 0.81-0.96, P = 0.004), with the statistically significant difference. The sensitivity analysis demonstrated the robustness of the PFS, ORR, and OS. Conclusion: The combination of PD-1/PD-L1 inhibitors with AAs in treating advanced patients has exhibited notable therapeutic advantages when contrasted with monotherapy. Specifically, the administration of PD-1/PD-L1 inhibitors in conjunction with AAs, or sequential treatment involving PD-1/PD-L1 followed by AAs, has shown enhanced therapeutic efficacy in this patient population.
ABSTRACT
Background: Currently, the anticancer effects of metformin on different types of lung cancer have been frequently studied. However, the relationship between metformin and prognosis in nondiabetic patients with lung cancer remains controversial. To systematically evaluate the efficacy of metformin adjunctive therapy as the treatment for nondiabetic patients with advanced non-small cell lung cancer (NSCLC) to provide an evidence-based reference for clinical medication. Materials and Methods: The literatures related to Phase II or III randomized controlled trials (RCTs) of metformin adjunctive therapy in nondiabetic patients with advanced NSCLC, including EMBASE, PubMed, the Cochrane Library, and Scopus database, were retrieved by computer, and the search time ranged from January 2017 to August 2022. The risk of bias assessment tool recommended by Cochrane Systematic Evaluator Manual 5.1.0 was used to evaluate the quality of the RCTs included. Rev Man 5.3 software and STATA15.0 were used for meta-analysis. Results: A total of 8 studies were included (925 patients). Meta-analysis results showed that there were no significant differences in progression-free survival (PFS) (hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.66-1.36, P = 0.77), overall survival (OS) (HR = 0.89, 95% CI: 0.61-1.30, P = 0.55, n =7), objective response rate (ORR) (odds ratio [OR] = 1.37, 95% CI: 0.76-2.46, P = 0.30), and 1-year PFS rate (OR = 0.87, 95% CI: 0.39-1.94, P = 0.73, n = 3). Sensitivity analysis showed that PFS and OS indexes were stable. Conclusion: Metformin adjunctive therapy can improve the DCR of nondiabetic patients with advanced NSCLC. In addition, the patients cannot obtain a prolonged PFS, OS, 1-year PFS rate, and higher ORR rate.
