TY - JOUR
T1 - Treatment-related toxicities of immune checkpoint inhibitors in advanced cancers: A meta-analysis
AU - Man, Johnathan
AU - Ritchie, Georgia
AU - Links, Matthew
AU - Lord, Sally
AU - Lee, Chee Khoon
N1 - Funding Information:
3National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Camperdown, NSW, Australia
Funding Information:
The authors acknowledge the editorial support provided by Ms Rhana Pike (NHMRC Clinical Trials Centre).
Publisher Copyright:
© 2018 John Wiley & Sons Australia, Ltd
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040722552&partnerID=8YFLogxK
U2 - 10.1111/ajco.12838
DO - 10.1111/ajco.12838
M3 - Article
C2 - 29349927
AN - SCOPUS:85040722552
SN - 1743-7555
VL - 14
SP - 141
EP - 152
JO - Asia-Pacific Journal of Clinical Oncology
JF - Asia-Pacific Journal of Clinical Oncology
IS - 3
ER -
