Sheng Zhang1, Fei Liang2, Wenfeng Li3, Qing Wang3. 1. Shanghai Cancer Center and Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: wozhangsheng@hotmail.com. 2. Shanghai Cancer Center and Shanghai Medical College, Fudan University, Shanghai, China. 3. The Affiliated Hospital of Qingdao University, Qingdao, China.
Abstract
BACKGROUND: Fatal adverse events (FAEs) have been reported in cancer patients receiving ipilimumab-a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, but the risk of treatment-related mortality is unknown. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of ipilimumab to determine the overall risk of FAEs associated with ipilimumab. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrial.gov and conference proceedings from inception to December 2016, for prospective trials that randomly assigned patients to ipilimumab treatment (with or without concurrent therapy) or controls with available data regarding incidence of FAEs. Two reviewers extracted data independently. Incidence of FAEs was pooled using a random effects model, and the risk of FAEs associated with ipilimumab was estimated using Peto odds ratios (ORs). RESULTS: A total of 5775 patients with solid tumours included in 12 RCTs (10 from journal reports and 2 from ClinicalTrials.gov) were included in the meta-analysis. The pooled incidence of FAEs for patients treated with ipilimumab was 1.13% (95% confidence interval [CI], 0.56-1.86), compared with 0.22% in the control arms. Ipilimumab was associated with statistically significantly increased risk of FAEs, with a pooled Peto OR of 2.3 (95% CI, 1.4-3.6; P < 0.001). Analyses according to cancer type (melanoma versus other cancers); treatment mode (combination therapy or monotherapy); control type (active control versus placebo/best supportive care only); ipilimumab dose (high versus low dose [10 versus 3 mg/kg every 3 weeks]) found no statistically significantly differential effect by subgroups. Among the specific causes of FAEs, ipilimumab was associated with an increased risk of fatal gastrointestinal toxicity, with an OR of 4.5 (95% CI, 1.5-13.6). CONCLUSION: The use of ipilimumab, compared with controls, was associated with increased risk of treatment-related mortality.
BACKGROUND: Fatal adverse events (FAEs) have been reported in cancerpatients receiving ipilimumab-a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, but the risk of treatment-related mortality is unknown. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) of ipilimumab to determine the overall risk of FAEs associated with ipilimumab. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrial.gov and conference proceedings from inception to December 2016, for prospective trials that randomly assigned patients to ipilimumab treatment (with or without concurrent therapy) or controls with available data regarding incidence of FAEs. Two reviewers extracted data independently. Incidence of FAEs was pooled using a random effects model, and the risk of FAEs associated with ipilimumab was estimated using Peto odds ratios (ORs). RESULTS: A total of 5775 patients with solid tumours included in 12 RCTs (10 from journal reports and 2 from ClinicalTrials.gov) were included in the meta-analysis. The pooled incidence of FAEs for patients treated with ipilimumab was 1.13% (95% confidence interval [CI], 0.56-1.86), compared with 0.22% in the control arms. Ipilimumab was associated with statistically significantly increased risk of FAEs, with a pooled Peto OR of 2.3 (95% CI, 1.4-3.6; P < 0.001). Analyses according to cancer type (melanoma versus other cancers); treatment mode (combination therapy or monotherapy); control type (active control versus placebo/best supportive care only); ipilimumab dose (high versus low dose [10 versus 3 mg/kg every 3 weeks]) found no statistically significantly differential effect by subgroups. Among the specific causes of FAEs, ipilimumab was associated with an increased risk of fatal gastrointestinal toxicity, with an OR of 4.5 (95% CI, 1.5-13.6). CONCLUSION: The use of ipilimumab, compared with controls, was associated with increased risk of treatment-related mortality.
Authors: Julie R Brahmer; Christina Lacchetti; Bryan J Schneider; Michael B Atkins; Kelly J Brassil; Jeffrey M Caterino; Ian Chau; Marc S Ernstoff; Jennifer M Gardner; Pamela Ginex; Sigrun Hallmeyer; Jennifer Holter Chakrabarty; Natasha B Leighl; Jennifer S Mammen; David F McDermott; Aung Naing; Loretta J Nastoupil; Tanyanika Phillips; Laura D Porter; Igor Puzanov; Cristina A Reichner; Bianca D Santomasso; Carole Seigel; Alexander Spira; Maria E Suarez-Almazor; Yinghong Wang; Jeffrey S Weber; Jedd D Wolchok; John A Thompson Journal: J Clin Oncol Date: 2018-02-14 Impact factor: 44.544