Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice.

A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule–Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects.

Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19–0.35, I² = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28–0.44; I² = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39–0.78, I² = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46–0.98, I² = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy.

Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.