Prognostic Evaluation Of Anti-PD-1/PD-L1 Immunotherapy

Objective: This study was aimed to evaluate the prognosis of solid tumor patients treated with anti-PD-1(anti-programmed cell death 1 receptor)/PD-L1(programmed cell death 1 ligand)immunotherapy compared with those who received chemotherapy using a real world study(RWS)and a meta-analysis based on randomized control trials.Methods:(1)The real world study was enrolled between January 1th,2017 and December 31 th,2017 within the following four hospital: Chinese PLA General Hospital(301 Hospital),Cancer Hospital Chinese Academy of Medical Sciences,Hubei Cancer Hospital and Cancer Center of Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology.All tumor patients who received anti-PD-1/PD-L1 immunotherapy with complete follow-up data were collected.The principle of 1:4 individual matching was conducted to collect controls patients treated with chemotherapy,which selected the control patients with the same sex,tumor type and tumor stage,age ± 5 year and therapy lines ± 1.Prognostic indicators included overall survival(OS),progression-free survival(PFS)and objective response rate(ORR).(2)The eligible studies were identified through searching PubMed,EMBASE,and Web of Science to systematically evaluate the efficacy and safety of anti-PD-1/PD-L1 immunotherapy by using meta-analysis.The prognostic indicators were the same as aforemented and the safety indicators consisted of any grade and grade three or above treatment-related adverse events(AEs).(3)Epidata 3.1 was applied to establish a database and SAS 9.3 software was used to conduct statistical analysis in the real world study.We compared the distribution of research factors in the two groups with Propensity Score Matching.The conditional logistic regression analysis was used to analyze the factors affecting the objective response rate,and the Cox regression analyses were used to analyze the factors affecting the program-free survival and overall survival.STATA SE version 12.0 was used for statistical analysis in meta-analysis.P value less than 0.05 was considered statistically significant.Results:(1)Becaused of the unachievable matching to 1:4 for two cases,we finally recruited 51 cancer patients treated with anti-PD-1/PD-L1 immunotherapy and 199 patients receiving chemotherapy were included in the real world study.Among all patients treated with anti-PD-1/PD-L1 immunotherapy,40 were males and 11 were females.Of patients receiving chemotherapy,160 were males and 39 were females.The number of lines of anti-PD-1/PD-L1 immunotherapy and corresponding chemotherapy(P < 0.001)and the resection status of primary lesion(P < 0.001)differed between the immunotherapy group and the chemotherapy group.Survival analysis showed that receiving anti-PD-1/PD-L1 immunotherapy was an independent prognostic factor of PFS(HR = 0.49,95% CI: 0.25-0.94)and able to increase the ORR in cancer patients(OR = 5.81,95% CI: 2.11-15.97).(2)Meta-analysis showed that compared with chemotherapy,anti-PD-1/PD-L1 immunotherapy presented significantly improved OS(HR = 0.68,95% CI: 0.64-0.73),PFS(HR = 0.67,95% CI: 0.59-0.77)and better ORR(OR = 3.03,95% CI: 2.33-3.94)in cancer patients.Subgroup analyses suggested profound efficacy of anti-PD-1/PD-L1 immunotherapy among patients with higher PD-L1 expression levels in tumors and under joint use with chemotherapy,especially as the first-line treatment.Furthermore,anti-PD-1/PD-L1 immunotherapy presented better safety than chemotherapy.Conclusions: Both of these two studies dedicated that compared with chemotherapy,anti-PD-1/PD-L1 immunotherapy may help to prolong the progress-free survival of cancer patients and improve objective response rate.Meta-analysis also showed that anti-PD-1/PD-L1 immunotherapy could provide better survival for patients with high PD-L1 expression levels and provide safety profiles.