Pembrolizumab alone or combined with chemotherapy versus chemotherapy for the treatment of metastatic cancer: A meta-analysis of randomized clinical trials

Background:Whether pembrolizumab alone or in combination with chemotherapy is superior to chemotherapy in metastatic cancer remains controversial. The study aims to give the effectiveness and safety of pembrolizumab-related interventions compared to chemotherapy in metastatic cancer. Methods:Electronic databases were systematically searched until November 20, 2023, for all randomized controlled trials comparing Pembrolizumab alone or in combination with chemotherapy versus chemotherapy for metastatic cancer. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and odds ratios with 95% confidence intervals (CI) were calculated for OS, PFS, overall response rate, and overall adverse events (AEs) by random effects models. Results:16 Randomized controlled trials with 9148 patients were included. Compared with chemotherapy, pembrolizumab was associated with longer OS (HR 0.82; 95% CI 0.73-0.91, P = .0004), more immune-mediated AEs, fewer overall AEs, and grade 3 or 4 AEs, however, no significant difference was found in PFS, overall response rate, and events leading to death. Pembrolizumab with chemotherapy was associated with longer OS (HR 0.74; 95% CI 0.61-0.90, P = .002) and PFS (HR 0.63; 95% CI 0.50-0.79, P < .0001), higher overall response rate, and more immune-mediated AEs comparing to chemotherapy alone, however, no significant advantages were observed in disease control rates, overall AEs, grade 3 or 4 AEs and events leading to death. The patients with programmed cell death ligand 1 tumor proportion scores of at least 50% or combined positive scores (CPS) of at least 10 could derive significantly better OS and PFS benefits from pembrolizumab alone or combined with chemotherapy. Similar OS results were found for first-line treatment and lung cancer subgroup analysis. Conclusions:Pembrolizumab alone or combined with chemotherapy indicates an effective and safe treatment for metastatic cancer. Pembrolizumab alone or combined with chemotherapy provides a better survival advantage under first-line treatment or programmed cell death ligand 1 combined positive scores of at least 10 or programmed cell death ligand 1 tumor proportion scores of at least 50%. However, we found that the specific efficacy of pembrolizumab in unused tumor types could not be effectively evaluated.