Meta-analysis: safety of immune checkpoint inhibitors in cancer

  • Wang Y & al.
  • JAMA Oncol
  • 25 Apr 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • 66.0% of patients with cancer receiving programmed cell death (PD-1) or PD-ligand 1 (PD-L1) inhibitors experience any grade and 14% experience grade ≥3 adverse events (AEs).
  • Immune related AEs are uncommon.
  • PD-1 inhibitors are associated with a higher risk for grade ≥3 AEs vs PD-L1 inhibitors.

Why this matters

  • This comprehensive summary of AEs can be useful in clinical practice.

Study design

  • Meta-analysis of 125 studies including 20,128 patients with cancer treated with single-agent PD-1/PD-L1 inhibitor.
  • Funding: None disclosed.

Key results

  • 66% of patients experienced any grade and 14% had grade ≥3 AEs; most common were:
    • all-grade: fatigue (18.26%); pruritus (10.61%).
    • grade ≥3: fatigue (0.89%); anemia (0.78%).
  • Most frequent immune-related endocrine AEs were:
    • all grade: hypothyroidism (6.07%); hyperthyroidism (2.82%); hyperglycemia (1.20%).
    • grade ≥3: hyperglycemia (0.24%); adrenal insufficiency (0.18%); type 1 diabetes (0.18%).
  • Other frequent immune-related AEs were:
    • all grade: diarrhea (9.47%); aspartate aminotransferase increase (AST; 3.39%); vitiligo (3.26%); alanine aminotransferase increase (ALT; 3.14%).
    • grade ≥3: AST increase (0.75%); ALT increase (0.70%).
  • Treatment-related death rate was 0.45%; pneumonitis was the most common cause.
  • PD-1 inhibitors were associated with a higher risk for grade ≥3 AEs vs PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).

Limitations

  • Publication bias.

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