Objective To systematically evaluate the benefits and safety of anti-PD-1/PD-L1 antibody in the treatment of advanced non-small cell lung cancer (NSCLC). Methods Randomized controlled trials (RCTs) about anti-PD-1/PD-L1 antibody versus conventional-dose chemotherapy in the treatment of advanced NSCLC were searched in PubMed, EMbase, The Cochrane Library (Issue 8, 2016), Web of Science, CBM, CNKI, and VIP databases from inception to September 2016. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of eligible studies, then meta-analysis was conducted by using RevMan 5.3 software. Results A total of five RCTs involving 2 580 patients were included. The results of meta-analysis showed that: the objective response rate (ORR) and one year overall survival rate (OSR1y) in anti PD-1/PD-L1 monoclonal antibody group were higher than that of the conventional chemotherapy group (RR=1.86, 95%CI 1.37 to 2.52,P<0.001; RR=1.37, 95%CI 1.23 to 1.52,P<0.001, respectively). However, there were no significant differences between two groups in one-year progression-free survival rate (PFSR1y) (RR=1.85, 95%CI 0.61 to 5.59,P=0.28) and disease control rate (DCR) (RR=1.13, 95%CI 0.76 to 1.68,P=0.55). With regard to untoward effect, rate of adverse effects (AEs) and AEs of 3-5 grade in anti PD-1/PD-L1 monoclonal antibody group were higher than those of the conventional chemotherapy group (RR=0.85, 95%CI 0.76 to 0.95,P=0.004; RR=0.28, 95%CI 0.18 to 0.43,P<0.001), the difference was statistically significant. But there was no significant difference in AEs to discontinuation between the two groups (RR=0.60, 95%CI 0.26 to 1.39,P=0.23). Conclusion Compared with conventional-dose chemotherapy, anti-PD-1/PD-L1 antibody has considerable current effect and safety in the treatment of advanced NSCLC.
ObjectivesTo systematically review the efficacy and safety of anti-PD-1/PD-L1 antibody in the treatment of advanced non-small cell lung cancer (NSCLC).MethodsNon-comparative binary data on anti-PD-1/PD-L1 monoclonal antibodies in the treatment of advanced NSCLC from PubMed, EMbase and The Cochrane Library databases were collected from inception to August 1st 2017. Two reviewers screened literature, extracted data and independently evaluated the risk of bias of included studies, then meta-analysis was conducted by RevMan 5.3 software.ResultsForty-four trials were included. The results of meta-analysis showed that the pooled objective response rate (ORR), overall 1-year survival rate (OSR1 year) and progression-free survival rate at 1 year (PFSR1 year ) of anti-PD-1/PD-1 antibodies were 22% (RD=0.22, 95%CI 0.20 to 0.25, P<0.001), 54% (RD=0.54, 95%CI 0.46 to 0.63,P<0.001) and 27% (RD=0.27, 95%CI 0.20 to 0.33,P<0.001), respectively. The rate of adverse effects (AEs) was 61% (RD=0.61, 95%CI 0.54 to 0.68,P<0.001), and the rate of grade 3 to 5 AEs was 13% (RD=0.13, 95%CI 0.10 to 0.15,P<0.001).ConclusionsAnti- PD-1/PD-1 antibodies show good efficacy and safety in the treatment of advanced NSCLC. Due to limited quality and quantity of included studies, more high-quality studies are needed to verify the above conclusions.
ObjectiveTo describe the research status of programmed death receptor protein 1 (PD-1) and its ligand(PD-L1) inhibitors in advanced gastric cancer and to understand the key issues of PD/PD-L1 inhibitors in order to provide atheoretical basis for future research.MethodThe classical and up to date literatures on the immunotherapy, especially thePD-1/PD-L1 inhibitors in the advanced gastric cancer were reviewed.ResultsThe PD-1/PD-L1 inhibitors were the hot spot in the current research of tumor immunotherapy. The pembrolizumab and nivolumab were the commonly immunosuppressive agents in the current clinical research, which had also achieved the great success in the clinical research of gastriccancer since it was shown the good results in the malignant melanoma and hematological malignancies. In some clinical studies, the PD-1/PD-L1 inhibitors treatment showed the longer overall survival than the conventional chemotherapy, especially in the patient with positive PD-1. However the study still had some issues to be solved, such as no accurate prediction for the beneficiary population, the tumor hyperprogression and so on. It was gratifying that the current research on the basic research of tumor immunity was increasing, then it provided a theoretical support for solving these problems.ConclusionsTumor immunosuppressive therapy such as PD-1/PD-L1 inhibitors brings a new idea in treatment of patients with advanced gastric cancer. Although there are still many problems need to be solved in clinical research, it is believed that PD-1/PD-L1 inhibitors will become one of key players in treatment of patients with advanced gastric cancer in the further study.
Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway has been found capable of affecting anti-tumor immune effect in many malignancies in recent years. Patients who are diagnosed with advanced non-small cell lung cancer (NSCLC) have considerable responses after receving inhibitors against PD-1/PD-L1. This paper reviews the clinical progress of PD-1/PD-L1 inhibitors in the treatment of NSCLC.
Objective To systematically evaluate the efficacy and safety of a combination regimen of PD-1/PD-L1 immune checkpoint inhibitors in the first-line treatment of advanced non-small cell lung cancer. Methods Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitor combination regimen in the first-line treatment of advanced non-squamous NSCLC were systematically retrieved from the Chinese and English electronic databases from inception to September 2023. The combination regimen includes PD-1/PD-L1 inhibitor+chemotherapy, PD-1/PD-L1 inhibitor+chemotherapy+anti-angiogenic agents (bevacizumab), and PD-1/PD-L1 inhibitor+CTLA4 inhibitor (ipilimumab). The network meta-analysis was performed using StataMP16.0 and R4.2.0 software. ResultsA total of 13 RCTs were collected, including 7 764 patients. In terms of effectiveness, compared with chemotherapy, several regimens improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Among them, toripalimab (Tor) plus chemotherapy (CT) may be associated with the best OS, and nivolumab plus bevacizumab and chemotherapy (Niv+Bev+CT) may provide the best PFS. Pembrolizumab (Pem) combined with CT was associated with the best treatment regimen for improving ORR. In terms of safety, except sintilimab (Sin) and Pem, the incidence of grade≥3 adverse events of all treatment regimens was significantly higher than that of chemotherapy (P<0.05). The incidence of AEs≥3 grade in Cam+CT was higher than that in Sin+CT (OR=0.44, 95%CI 0.25-0.80) and Pem+CT (OR=0.52, 95%CI 0.31-0.88). And the incidence of ≥3grade AEs in Atezolizumab (Ate) +Bev+CT (OR=2.32, 95%CI 1.14-4.71; OR=1.97, 95%CI 1.02-3.79) was also higher than that in Sin+CT and Pem+CT (P<0.05). Conclusion In non-squamous NSCLC patients, PD-1 inhibitor combined with chemotherapy can bring more benefits to advanced NSCLC patients than chemotherapy alone.
ObjectiveTo investigate the relationship between the expression of programmed cell death ligand-1 (PD-L1) and the maximal standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the correlation of clinical factors between SUVmax values and PD-L1.MethodsThe clinical data of 84 patients with invasive lung adenocarcinoma diagnosed pathologically in West China Hospital, Sichuan University from August 2016 to November 2018 were analyzed retrospectively, including 38 males and 46 females, aged 60 (32-85) years. The tumor was acinar-predominant in 37 patients, papillary in 20, lepidic in 19, solid in 5 and micropapillary in 3. Multivariate analysis of the relationship between SUVmax value and other clinicopathological features was performed by linear regression. Logistic regression analysis was used to analyze the relationship between PD-L1 protein expression and other pathological features.ResultsThe SUVmax of the PD-L1 expression group was significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group (P=0.002) and intermediate-grade histologic subtype (P=0.016). The SUVmax cut-off value of PD-L1 expression in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype was 5.34 (AUC: 0.732, P=0.002) and 5.34 (AUC: 0.720, P=0.017), respectively. Multivariate analysis showed that pleura involvement, vascular tumor thrombus and the increase of tumor diameter could cause the increase of the SUVmax value, while the SUVmax value decreased in the moderately differentiated tumor compared with the poorly differentiated tumor. The SUVmax cut-off value between low-grade histologic subtype and intermediate-grade histologic subtype, intermediate-grade histologic subtype and high-grade histologic subtypes was 1.54 (AUC: 0.854, P<0.001) and 5.79 (AUC: 0.889, P<0.001), respectively. Multivariate analysis of PD-L1 expression showed pleura involvement (P=0.021, OR=0.022, 95%CI 0.001 to 0.558) and moderate differentiation (opposite to poor differentiation) (P=0.004, OR=0.053, 95%CI 0.007 to 0.042) decreased the expression of PD-L1.ConclusionThe SUVmax of the PD-L1 expression group is significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype. The level of SUVmax and the expression of PD-L1 in invasive lung adenocarcinoma are related to many clinical factors.
Lung cancer is the most frequent cancer and the leading cause of cancer death all around the world. Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapies have significantly improved the outcomes of non-small cell lung cancer (NSCLC) patients in recent years. However, the objective response rate in non-screened patients is only about 20%. It is very important to screen out the potential patients suitable for immunotherapy. Immunohistochemical staining of tumor tissue biopsies with PD-L1 antibodies can predict the therapeutic response to immunotherapy to some extent, but it still has some limitations. Recently some clinical studies have shown that PD-L1 expression in circulating tumor cells (CTC-PD-L1) is a potential independent biomarker and may provide important information for immunotherapy in NSCLC. This article will review technology for CTC-PD-L1 detection and the predictive value of CTC-PD-L1 for immunotherapy in NSCLC and review the latest clinical research progress.
ObjectiveTo systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis.MethodsThe literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis.Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.0001).ConclusionPD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.
Lung cancer is the leading cause of cancer-related deaths worldwide. Although improvement has been achieved in platinum-based chemotherapy and tyrosine kinase inhibitors-based molecular targeted therapy, they still have limitations. Immunotherapy has recently emerged as a very effective new treatment, and there is now growing enthusiasm in cancer immunotherapy worldwide. We summarized the effects of immune checkpoint inhibitors in clinical trials, and the current status and progress of anti programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) agents in lung cancer treatment. Attention has been paid to finding out the factors which influence the therapeutic effect of anti-PD-1/PD-L1 therapy and reducing the occurrence of adverse events.
Objective To systematically evaluate the effect and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy for resectable non-small cell lung cancer (NSCLC). Methods The PubMed, EMbase, The Cochrane Library, CNKI, and Wanfang data were searched by computer to identify relevant studies on anti PD-1 /PD-L1 combined with chemotherapy for resectable NSCLC from inception to March 2023. Two authors independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. The single-arm study was evaluated for quality using the methodological index for non-randomized studies (MINORS). Meta-analysis was conducted by RevMan 5.4 software. Results Twenty-six studies with 965 patients were included in this meta-analysis. MINORS scores of single-arm studies were ≥12 points. The meta-analysis results showed that the pooled pathologic complete response, major pathologic response, and objective response rates as well as partial response, surgical rate and R0 surgical resection rate of neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy were 39% [RD=0.39, 95%CI (0.31, 0.47) ], 59% [RD=0.59, 95%CI (0.53, 0.65) ], 72% [RD=0.72, 95%CI (0.65, 0.80) ], 62% [RD=0.62, 95%CI (0.56, 0.69) ], 86% [RD=0.86, 95%CI (0.81, 0.92) ], and 94% [RD=0.94, 95%CI (0.92, 0.97) ], respectively. In terms of safety, the rate of adverse events (AEs) was 65% [RD=0.65, 95%CI (0.52, 0.78) ], and the rate of grade 3 to 5 AEs was 16% [RD=0.16, 95%CI (0.10, 0.23) ]. Conclusion The combination of neoadjuvant PD-1/PD-L1 inhibitors with chemotherapy has good efficacy and safety in the treatment of patients with resectable NSCLC.