TY - JOUR
T1 - Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors
T2 - a systematic review and meta-analysis of randomized clinical trials
AU - Magee, D. E.
AU - Hird, A. E.
AU - Klaassen, Z.
AU - Sridhar, S. S.
AU - Nam, R. K.
AU - Wallis, C. J.D.
AU - Kulkarni, G. S.
N1 - Publisher Copyright:
© 2019 European Society for Medical Oncology
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - adverse events
KW - chemotherapy
KW - immunotherapy
KW - meta-analysis
KW - neoplasm
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UR - http://www.scopus.com/inward/citedby.url?scp=85077692403&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2019.10.008
DO - 10.1016/j.annonc.2019.10.008
M3 - Review article
C2 - 31912796
AN - SCOPUS:85077692403
SN - 0923-7534
VL - 31
SP - 50
EP - 60
JO - Annals of Oncology
JF - Annals of Oncology
IS - 1
ER -