Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials

D. E. Magee, A. E. Hird, Z. Klaassen, S. S. Sridhar, R. K. Nam, C. J.D. Wallis, G. S. Kulkarni

Research output: Contribution to journalReview article

3 Scopus citations


Background: 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. Design: 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. Results: 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. Conclusions: Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.

Original languageEnglish (US)
Pages (from-to)50-60
Number of pages11
JournalAnnals of Oncology
Issue number1
StatePublished - Jan 2020



  • adverse events
  • chemotherapy
  • immunotherapy
  • meta-analysis
  • neoplasm

ASJC Scopus subject areas

  • Hematology
  • Oncology

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