Qiang Su1, Xiao-Chen Zhang2, Di-Ya Wang3, Huai-Rong Zhang4, Cheng Zhu5, Yan-Li Hou6, Jun-Li Liu7, Zu-Hua Gao8. 1. Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: qiang.su@mail.mcgill.ca. 2. School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: zhang-xc13@mails.tsinghua.edu.cn. 3. Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montreal, Quebec H2X 0A9, Canada. 4. Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shanxi, China. Electronic address: huairong.zhang@mail.mcgill.ca. 5. Desautels Faculty of Management, McGill University, Canada. Electronic address: cheng.zhu@mail.mcgill.ca. 6. Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: yanli.hou@mail.mcgill.ca. 7. Department of Pathology, Research Institute of McGill University Health Center, Montreal, Quebec, Canada. Electronic address: jun-li.liu@mcgill.ca. 8. Department of Pathology, Research Institute of McGill University Health Center, Montreal, Quebec, Canada. Electronic address: zu-hua.gao@mcgill.ca.
Abstract
BACKGROUND: We performed a systematic review and meta-analysis to evaluate the risk of immune-related endocrine disorders associated with PD-1 inhibitors therapy for solid tumors. METHODS: An Embase and PubMed search through December 6, 2017, using the following keywords was performed: immune-related endocrine disorders, and PD-1 inhibitors, etc. The data were analyzed using R 3.4.3 (R Project) and the metafor package. Patients treated with chemotherapy alone were used as control for the purpose of comparison. RESULTS: A total of 12 clinical trials including 5577 patients were found eligible for the meta-analysis. Compared with chemotherapy, the risk ratios of all-grade endocrine disorders are 13.89, (95% CI: 5.35-36.05, p < 0.001) for nivolumab therapy, and 9.85, (95% CI: 5.65-17.17, p < 0.001) for pembrolizumab therapy. The risk of all-grade hypothyroidism and hyperthyroidism incidence was increased for nivolumab therapy (hypothyroidism: RR 10.07, 95% CI: 3.37-30.11, p < 0.001; hyperthyroidism: RR 4.29, 95% CI: 1.13-16.30, p = 0.034) and for pembrolizumab therapy (hypothyroidism: RR 7.73, 95% CI: 3.86-15.49, p < 0.001; hyperthyroidism: RR 5.09, 95% CI: 2.36-10.97, p < 0.001). There was a significant increase in the risk of grade 1-5 endocrine disorders incidence for ipilimumab-nivolumab combination therapy (versus ipilimumab, RR 3.20, 95% CI: 2.08-4.91, p < 0.001; versus nivolumab, RR 2.54, 95% CI: 1.70-3.80, p < 0.001). CONCLUSIONS: Both nivolumab and pembrolizumab therapy could result in a higher risk of all-grade immune-related endocrine disorders than chemotherapy. Nivolumab and ipilimumab combination therapy could result in an even higher risk of all-grade immune-related endocrine disorders than ipilimumab or nivolumab alone. Awareness of these side effects could guide clinicians to better manage the patients treated with anti-PD-1 inhibitors therapy for solid tumors.
BACKGROUND: We performed a systematic review and meta-analysis to evaluate the risk of immune-related endocrine disorders associated with PD-1 inhibitors therapy for solid tumors. METHODS: An Embase and PubMed search through December 6, 2017, using the following keywords was performed: immune-related endocrine disorders, and PD-1 inhibitors, etc. The data were analyzed using R 3.4.3 (R Project) and the metafor package. Patients treated with chemotherapy alone were used as control for the purpose of comparison. RESULTS: A total of 12 clinical trials including 5577 patients were found eligible for the meta-analysis. Compared with chemotherapy, the risk ratios of all-grade endocrine disorders are 13.89, (95% CI: 5.35-36.05, p < 0.001) for nivolumab therapy, and 9.85, (95% CI: 5.65-17.17, p < 0.001) for pembrolizumab therapy. The risk of all-grade hypothyroidism and hyperthyroidism incidence was increased for nivolumab therapy (hypothyroidism: RR 10.07, 95% CI: 3.37-30.11, p < 0.001; hyperthyroidism: RR 4.29, 95% CI: 1.13-16.30, p = 0.034) and for pembrolizumab therapy (hypothyroidism: RR 7.73, 95% CI: 3.86-15.49, p < 0.001; hyperthyroidism: RR 5.09, 95% CI: 2.36-10.97, p < 0.001). There was a significant increase in the risk of grade 1-5 endocrine disorders incidence for ipilimumab-nivolumab combination therapy (versus ipilimumab, RR 3.20, 95% CI: 2.08-4.91, p < 0.001; versus nivolumab, RR 2.54, 95% CI: 1.70-3.80, p < 0.001). CONCLUSIONS: Both nivolumab and pembrolizumab therapy could result in a higher risk of all-grade immune-related endocrine disorders than chemotherapy. Nivolumab and ipilimumab combination therapy could result in an even higher risk of all-grade immune-related endocrine disorders than ipilimumab or nivolumab alone. Awareness of these side effects could guide clinicians to better manage the patients treated with anti-PD-1 inhibitors therapy for solid tumors.
Authors: L Brilli; R Danielli; M Campanile; C Secchi; C Ciuoli; L Calabrò; T Pilli; A Cartocci; F Pacini; A M Di Giacomo; M G Castagna Journal: J Endocrinol Invest Date: 2020-12-26 Impact factor: 4.256