Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.
Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Int J Environ Res Public Health. 2022 Jul 27;19(15):9196. doi: 10.3390/ijerph19159196.
Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.
尽管靶向治疗联合化疗的严重不良事件 (SAE) 风险显著升高，但全面的药物警戒研究仍很有限。本研究旨在系统评估 RAS 野生型转移性结直肠癌患者常用靶向药物（贝伐珠单抗、西妥昔单抗和帕尼单抗）的 SAE 风险。按照 PRISMA-NMA 指南对 Cochrane Library、ClinicalKey 和 MEDLINE 进行关键词检索。对 8 项随机对照试验进行了频率论网络荟萃分析，以比较 21 种 SAE 谱的相对风险 (RR)。靶向药物的血液学、胃肠道和神经 SAE 风险无显著性差异（p>0.05）。贝伐珠单抗联合化疗的严重高血压风险显著升高（p<0.05），而帕尼单抗联合化疗的严重血栓栓塞风险显著升高（RR 3.65；95%CI 1.30−10.26）。尽管西妥昔单抗和帕尼单抗均显示出严重皮肤毒性和肾脏毒性的风险增加，但帕尼单抗联合化疗的皮肤毒性（RR 15.22；95%CI 7.17−32.35）、黏膜炎（RR 3.18；95%CI 1.52−6.65）、低镁血症（RR 20.10；95%CI 5.92−68.21）和脱水（RR 2.81；95%CI 1.03−7.67）的风险相对更高。因此，有必要进一步研究风险分层和 SAE 管理，以确保靶向药物的安全使用。
