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Treatment‐related toxicities of immune checkpoint inhibitors in advanced cancers: A meta‐analysis
Author(s) -
Man Johnathan,
Ritchie Georgia,
Links Matthew,
Lord Sally,
Lee Chee Khoon
Publication year - 2018
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12838
Subject(s) - medicine , discontinuation , chemotherapy , pneumonitis , adverse effect , gastroenterology , neutropenia , rash , toxicity , oncology , lung
Abstract Background We performed a meta‐analysis to quantify toxic death, adverse events (AEs) and treatment discontinuation due to AEs from checkpoint inhibitors (CI). Methods 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. Results 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. Conclusions CI inhibitors have different toxicity profiles to chemotherapy. These findings are useful for patient counselling and planning of future trials.