Evidence-based Assessment Of PD-1/PD-L1 Inhibitors In The Treatment Of Malignant Tumors

Objective:This study aims to overview the clinical benefits of PD-1/PD-L1 inhibitors in the treatment of malignant tumors based on evidence,and to provide reference for clinical application of PD-1/PD-L1 inhibitors.Methods:(1)Systematic reviews of PD-1/PD-L1 inhibitors on malignant tumors were searched according to inclusion criteria and exclusion criteria.Two researchers independently extracted data and assessed the report quality,methodological quality and quality of evidence by PRISMA statement,AMSTAR 2 and GRADE guidelines,and analyzed qualitative evidence.(2)Assessed the value of cancer types with conflicting evidence based on the results of overview of systematic reviews,RCTs of PD-1/PD-L1 inhibitors in the treatment of esophageal and gastrointestinal cancers were included.ASCO-VF and ESMO-MCBS were used to assess the value of PD-1/PD-L1 inhibitors.The relationship between the value of PD-1/PD-L1 inhibitors and incremental monthly cost was explored by Spearman’s correlation method.Results:(1)172 systematic reviews meeting the inclusion criteria were included.The report quality of included systematic reviews was good,with 128(74.42%)high quality reports and 44(25.58%)moderate quality reports.The methodological quality of the included systematic reviews was generally poor,with only 1(0.58%)systematic reviews of high quality,5(2.91%)low quality,and 166(96.51%)critically low quality.The results of the GRADE guidelines evaluation showed that 38(3.77%)outcome indicators had high quality,288(28.57%)moderate quality,545(54.07%)low quality,and 137(13.59%)critically low quality.Current evidence showed that PD-1/PD-L1 inhibitors were significantly more effective than conventional chemotherapy in the treatment of NSCLC,small cell lung cancer,renal cell carcinoma,malignant melanoma,hepatocellular carcinoma,head and neck squamous cell carcinoma and urothelial carcinoma,breast cancerwith PD-L1 expression level≥1%.However,the evidence is inconsistent in esophageal and gastrointestinal cancers.(2)33 literatures reported 23 randomized controlled trials were identified: ten(43.48%)in esophageal cancer,five(21.74%)in colorectal cancer,and eight(34.78%)in gastroesophageal junction cancer.ASCO-VF scores ranged from-12.5 to 69,with a mean score of 26.5(95% CI18.4-34.6).6(42.9%)therapeutic regimens met the ESMO-MCBS benefit threshold grade.ASCO-VF scores was negatively correlated with incremental monthly cost(Spearman’s ρ=-0.465,P=0.034).ESMO-MCBS grades was negatively correlated with incremental monthly cost(Spearman’s ρ=-0.211,P=0.489).Conclusions: A large amount of low-quality evidence has shown the efficacy of PD-1/PD-L1 inhibitors on malignant tumor except esophageal and gastrointestinal cancers.And we shoud pay an attention on the occurrence of ir AEs.PD-1/PD-L1 inhibitors have no clinical benefit on gastroesophageal junction cancer,while pembrolizumab monotherapy has value on advanced first-line microsatellite instability–high colorectal cancer.Camrelizumab and toripalimab may be valuable for advanced esophageal cancer.