Cheng Ryan, Boparai Montek, Zhu Xiaolei, Wu Shenhong
Renaissance School of Medicine, Stony Brook University, Stony Brook, New York, USA.
Division of Nephrology, Department of Medicine, Stony Brook University Hospital, Stony Brook, New York, USA.
Cancer Invest. 2025 May;43(5):293-304. doi: 10.1080/07357907.2025.2502992. Epub 2025 May 13.
Enfortumab vedotin, an anti-nectin-4 antibody-drug conjugate, is a key treatment for advanced urothelial cancer. However, hyperglycemia, a major adverse event, varies in incidence and can progress to diabetic ketoacidosis. We conducted a systematic review and meta-analysis to quantify the risk of hyperglycemia with enfortumab vedotin.
We searched studies published through September 30, 2024. Eligible clinical trials evaluated enfortumab vedotin as a monotherapy or combined with pembrolizumab. Pooled incidence and relative risk of hyperglycemia were calculated using random- or fixed-effects models.
Seven studies with 2,138 patients were included in our analysis. The summary incidence of all-grade hyperglycemia was 10.3% (95% CI: 8.6-12.2%), and high-grade hyperglycemia occurred in 5.7% (95% CI: 4.5-7.1%) of patients. No significant difference was observed between monotherapy and combination therapy ( = 0.16). Enfortumab vedotin significantly increased the risk of all-grade (RR = 16.97, 95% CI: 6.22-48.25, < 0.001) and high-grade hyperglycemia (RR = 34.78, 95% CI: 4.77-253.43, < 0.001).
Enfortumab vedotin is associated with a significantly increased risk of all-grade and high-grade hyperglycemia in urothelial cancer. Its combination with pembrolizumab does not appear to elevate this risk further. Routine glucose monitoring and early intervention should be implemented, particularly in high-risk patients.
恩杂鲁胺维托辛是一种抗Nectin-4抗体药物偶联物，是晚期尿路上皮癌的关键治疗药物。然而，高血糖作为一种主要不良事件，其发生率各不相同，且可能进展为糖尿病酮症酸中毒。我们进行了一项系统评价和荟萃分析，以量化恩杂鲁胺维托辛导致高血糖的风险。
我们检索了截至2024年9月30日发表的研究。符合条件的临床试验评估了恩杂鲁胺维托辛作为单一疗法或与帕博利珠单抗联合使用的情况。使用随机或固定效应模型计算高血糖的合并发生率和相对风险。
我们的分析纳入了7项研究，共2138例患者。所有级别的高血糖汇总发生率为10.3%（95%置信区间：8.6-12.2%），5.7%（95%置信区间：4.5-7.1%）的患者发生了高级别高血糖。单一疗法和联合疗法之间未观察到显著差异（P = 0.16）。恩杂鲁胺维托辛显著增加了所有级别（相对风险=16.97，95%置信区间：6.22-48.25，P<0.001）和高级别高血糖（相对风险=34.78，95%置信区间：4.77-253.43，P<0.001）的风险。
恩杂鲁胺维托辛与尿路上皮癌患者所有级别和高级别高血糖风险的显著增加相关。它与帕博利珠单抗联合使用似乎不会进一步提高这种风险。应实施常规血糖监测和早期干预，尤其是在高危患者中。
