Treatment-related toxicities of immune checkpoint inhibitors in advanced cancers: A meta-analysis

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We performed a meta-analysis to quantify toxic death, adverse events (AEs) and treatment discontinuation due to AEs from checkpoint inhibitors (CI).


We searched for randomized trials with adequate reporting for toxicity outcomes. Pooled risk ratios were estimated for CI versus chemotherapy or different combinations of these agents.


Twenty trials of five different cancers with 10 794 patients with performance status 0 or 1 were identified. Toxic deaths from CI were infrequent (0.6%). Treatment discontinuations were less frequent for programmed-death-1 (PD-1) or PD-ligand-1 (PD-L1) inhibitors (5.8% vs 13.3%, P < 0.001) and cytotoxic-T-lymphocyte-associated-antigen-4 (CTLA-4) inhibitors (6.2% vs 11.4%, P = 0.002) than chemotherapy. PD-1/PD-L1 inhibitors had less grade 3, 4, and 5 (G3/4/5) AEs than chemotherapy (13.8% vs 39.8%, P < 0.001) or CTLA-4 inhibitors (13.4% vs 22.8%, P < 0.001). Combination CI had higher discontinuation (37.8% vs 11.6%, P < 0.001) and higher G3/4/5 AEs (55.3% vs 21.9%, P < 0.001) than CI monotherapy. Endocrinopathy (11.2% vs 0.9%), rash (10.1% vs 4.3%) and pneumonitis (3.1% vs 0.7%) were associated with CI, and alopecia (25.9% vs 1.0%), neutropenia (16.6% vs 0.6%) and neuropathy (7.6% vs 3.0%) with chemotherapy.


CI inhibitors have different toxicity profiles to chemotherapy. These findings are useful for patient counselling and planning of future trials.

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