CE3 Systematic Review and Indirect Comparison of PD-(L)1 Inhibitors in Combination with Platinum-Based Doublet Chemotherapy (PT-DC) for the First-Line Treatment of Non-Squamous, Non-Small-Cell Lung Cancer (nsqNSCLC)


      To evaluate relative efficacy and safety of sintilimab compared with other PD-(L)1 inhibitors in combination with platinum-based doublet chemotherapy (PT-DC) for the first-line treatment of nsqNSCLC.


      A systematic literature search was conducted based on published studies in electronic databases up to December 2020. Eligible randomized controlled trials (RCT) that investigated untreated locally advanced or metastatic nsqNSCLC without activating EGFR mutations or ALK translocations patients were analyzed. Outcomes evaluated by adjusted indirect treatment comparison (ITC) using Bucher method mainly included progression-free survival (PFS), objective response rate (ORR), time to response (TTR) and safety profile. Taking the heterogeneity into account, random-effect model will be applied if the p-value of Chi-square test greater than 0.05.


      Seven RCTs involving 3,559 patients were included. ITC results suggested that combined PT-DC with sintilimab had a comparable PFS compared with that of combined PT-DC with pembrolizumab (HR=1.00, 95%CI: 0.71 to 1.41), atezolizumab (HR=0.81, 95%CI: 0.59 to 1.10), tislelizumab (HR= 0.75, 95%CI: 0.48 to 1.16), camrelizumab (HR=0.80, 95%CI:0.54 to 1.20) and nivolumab (HR=0.72, 95%CI : 0.51 to 1.02). Little differences were found in ORR between combined PT-DC with sintilimab and combined PT-DC with pembrolizumab (OR=0.66, 95%CI: 0.37 to 1.20), atezolizumab (OR=1.23, 95%CI: 0.70 to 2.14), tislelizumab (OR=1.11, 95%CI: 0.58 to 2.11), camrelizumab (OR=1.05, 95%CI: 0.58 to 1.90) and nivolumab (OR=1.14, 95%CI: 0.64 to 2.00). Incidence of all grades or grades ≥3 adverse events (AE) were comparable between combined PT-DC with sintilimab and other PD-(L)1s. For AE leading to discontinuation, the incidence of sintilimab in combination with PT-DC is significantly lower than that of pembrolizumab in combination with PT-DC (OR=0.27, 95%CI: 0.11 to 0.67).


      Combined PT-DC with sintilimab and other PD-(L)1 inhibitors had comparable efficacy and safety profile for the first-line treatment of locally advanced or metastatic nsqNSCLC patients.