Efficacy and safety of anti-PD-1/PD-L1 combinations versus standard of care in cancer: a systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) as monotherapy in different solid tumors showed an early detrimental effect in a subset of patients reflected by the early crossover of the progression-free survival (PFS) curves. Currently, combination therapies with ICIs added to chemotherapy or targeted therapy are expanding the landscape of metastatic solid tumors. We have examined the benefits and risks of adding ICIs to the standard of care (SOC) versus SOC alone. A search of randomized clinical trials (RCTs) comparing ICIs combinations versus the corresponding SOC in different metastatic tumors according to the PRISMA guidelines was performed. Selected endpoints included PFS, time-to-response (TTR), overall survival (OS), overall response rate (ORR), and ≥ grade 3 adverse events (AEs). Subgroup analyses based on backbone treatment and tumor type were included. A total of 10536 patients (19 studies) were included (ICIs-arm: 5596 patients; SOC-arm: 4940 patients). Globally, PFS, OS, and ORR results favored ICIs-arm. No differences in terms of TTR were found between arms. ICI-arm was associated with a slight increase of ≥ G3 AEs (relative risk: 1.07). The results in multiple myeloma patients are controversial in favor of ICIs combinations. Adding ICIs to SOC benefits a greater number of patients, prolonging survival with no early detrimental effect. The toxicity profile is safe, with a mild increase of high-grade manageable AEs.