Objective: This study aimed to compare the efficacy and safety between sintilimab combinations and single treatment in cancer patients, as well as identify biomarkers for selection of patients who might benefit from the combination treatments.
Materials and methods: A search of randomized clinical trials (RCTs) comparing sintilimab combinations vs. single treatment in different tumors according to the PRISMA guidelines was performed. Selected endpoints included completion response rate (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), major adverse effects (AEs), immune-related adverse events (irAEs). Subgroup analyses based on different combination regimens, tumor type and basic biomarkers were included.
Results: Results reported from 11 RCTs involving 2,248 patients were included in this analysis. Pooled results indicated that both sintilimab plus chemotherapy and sintilimab plus targeted therapy significantly improved CR [RR=2.44, 95% CI (1.14, 5.20), p=0.021; RR=2.91, 95% CI (1.29, 6.57), p=0.010], ORR [RR=1.34, 95% CI (1.13, 1.59), p=0.001; RR=1.70, 95% CI (1.13, 2.56), p=0.011], PFS [HR=0.56, 95% CI (0.43, 0.69), p<0.001; HR=0.56, 95% CI (0.49, 0.64), p<0.001] and OS [HR=0.59, 95% CI (0.48, 0.70), p<0.001]. Subgroup analyses suggested that the sintilimab-chemotherapy group exhibited a superior PFS benefit than the chemotherapy alone group regardless of age, gender, EGOS PS, PD-L1 expression, smoking status, and clinical stage. There were no significant statistical differences in the incidence of any grade and grade 3 or worse AEs between the two groups [RR=1.00, 95% CI (0.91, 1.10), p=0.991; RR=1.06, 95% CI (0.94, 1.20), p=0.352]. While the incidence of any grade irAEs was higher with sintilimab plus chemotherapy as compared to chemotherapy alone (RR=1.24, 95% CI (1.01, 1.54), p=0.044), but no significant difference was found for grade 3 or worse irAEs (RR=1.11, 95% CI (0.60, 2.03), p=0.741).
Conclusions: Sintilimab combinations brought benefits to a greater number of patients at the cost of a mild increase of irAEs. PD-L1 expression may not be used as a predictive biomarker, composite biomarkers consisting of PD-L1 and MHC class II expression are worth to be explored to enlarge the patient population that benefits from sintilimab combinations.