TY - JOUR
T1 - Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors
T2 - A systematic review and meta-analysis of randomized clinical trials
AU - Costa, Ricardo
AU - Carneiro, Benedito A.
AU - Agulnik, Mark
AU - Rademaker, Alfred W.
AU - Pai, Sachin G.
AU - Villaflor, Victoria M.
AU - Cristofanilli, Massimo
AU - Sosman, Jeffrey A.
AU - Giles, Francis Joseph
PY - 2017
Y1 - 2017
N2 - Purpose: Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents. Methods: PubMed search was conducted in February of 2016. The randomized trials needed to have at least one of the study arms consisting of nivolumab or pembrolizumab monotherapy and a control arm containing no anti-PD-1 therapy. Data were analyzed using random effects meta-analysis for risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics. Results: Nine randomized trials and 5,353 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies. The pooled relative risk (RR) for treatment-related all grade AEs and grade 3/4 AEs was 0.88 (95% CI 0.81-0.95;P=0.002) and 0.39 (95% CI 0.29-0.53; P<0.001) respectively favoring anti-PD-1 therapy versus standard of care approach. The RR of treatment-related death was 0.45 (95% CI 0.19-1.09; P=0.076). Patients treated with PD-1 inhibitors had an increased risk of hyperthyroidism [RR of 3.44 (95% CI 1.98-5.99; P<0.001)] and hypothyroidism [RR of 6.79 (95% CI 3.10-14.84; P<0.001)]. All grade pruritus and vitiligo were also more common among these patients. The pooled absolute risks of pneumonitis and hypophysitis were 2.65% and 0.47% respectively. Conclusion: Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo.
AB - Purpose: Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents. Methods: PubMed search was conducted in February of 2016. The randomized trials needed to have at least one of the study arms consisting of nivolumab or pembrolizumab monotherapy and a control arm containing no anti-PD-1 therapy. Data were analyzed using random effects meta-analysis for risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics. Results: Nine randomized trials and 5,353 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies. The pooled relative risk (RR) for treatment-related all grade AEs and grade 3/4 AEs was 0.88 (95% CI 0.81-0.95;P=0.002) and 0.39 (95% CI 0.29-0.53; P<0.001) respectively favoring anti-PD-1 therapy versus standard of care approach. The RR of treatment-related death was 0.45 (95% CI 0.19-1.09; P=0.076). Patients treated with PD-1 inhibitors had an increased risk of hyperthyroidism [RR of 3.44 (95% CI 1.98-5.99; P<0.001)] and hypothyroidism [RR of 6.79 (95% CI 3.10-14.84; P<0.001)]. All grade pruritus and vitiligo were also more common among these patients. The pooled absolute risks of pneumonitis and hypophysitis were 2.65% and 0.47% respectively. Conclusion: Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo.
KW - Adverse events
KW - Anti-PD1 antibodies
KW - Hypothyroidism
KW - Meta-analysis
KW - Pruritus
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U2 - 10.18632/oncotarget.13315
DO - 10.18632/oncotarget.13315
M3 - Review article
C2 - 27852042
AN - SCOPUS:85059025761
VL - 8
SP - 8910
EP - 8920
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 5
ER -