Background and Objective:
Nivolumab and
Ipilimumab are
immune checkpoint inhibitors. The combination of
Nivolumab and
Ipilimumab has been reported to have complementary effects in the treatment of metastatic
melanoma. The combination
therapy of
Nivolumab and
Ipilimumab (N+I) has shown synergistic effects in
cancer immunotherapy but this is still controversial due to the higher incidence of toxicity. Hence, we conducted a meta-analysis to evaluate the efficacy and safety profile of
Nivolumab combined with
Ipilimumab and compared the different dosing schedules of the N+I combination.Methods: By searching in PubMed, PMC, Cochrane library and major conference abstracts, eligible sixteen studies including N+I
therapy and
Nivolumab monotherapy were selected to analyze overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and high-grade (3-4) adverse effects (AEs). Results: Compared with monotherapy of
Nivolumab, N+I significantly improved ORR (RR=1.40 [95% CI 1.27, 1.54], P<0.00001) and PFS (Hazard Ratio (HR)=0.83 [95% CI 0.77, 0.90], P<0.00001), but not OS (HR=0.93 [95% CI 0.84, 1.03], P=0.16). In a sub-analysis, the combination of
Nivolumab 1mg/kg plus
Ipilimumab 3mg/kg (N1I3) and
Nivolumab 3mg/kg plus
Ipilimumab 1mg/kg (N3I1) achieved better ORR and PFS than
Nivolumab 3mg/kg (N3) alone. Remarkably, OS was also prolonged with the N1I3 combination compared with the N3I1 combination or N3. Furthermore, a higher incidence of high-grade AEs also occurred with the combination
therapy of N1I3.Conclusions: N+I combination
therapy showed greater ORR and PFS compared with
Nivolumab monotherapy. N1I3 combination provided the benefit of ORR, PFS and OS but was associated with a higher incidence of toxicity.