Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies

作者：Li, J.; Cheng, Y.; Bai, C.^*; Xu, J.^*; Shen, L.^*; Zhou, Z.; Li, Z.; Chi, Y.; Yu, X.; Li, E.; Xu, N.; Liu, T.; Lou, W.; Bai, Y.; Yuan, X.; Wang, X.; Yuan, Y.; Chen, J.; Guan, S.; Fan, S.; Su, W.

来源：ESMO Open, 2022, 7(2): 100453.

DOI：10.1016/j.esmoop.2022.100453

• neuroendocrine tumor
• surufatinib
• SANET
• biomarker
• adverse event

Background: No validated biomarkers currently exist for predicting the efficacy outcomes in patients with neuroendocrine tumors (NETs) treated with antiangiogenic therapy. We aimed to evaluate the association between treatment-related adverse events (TRAEs) and efficacy outcomes of surufatinib in patients with advanced NET. @@@ Patients and methods: We included patients with NET treated with surufatinib in two multicenter, randomized, double-blind, placebo-controlled, phase III trials (SANET-p and SANET-ep) in this study. The main exposure was the presence of any of the TRAEs including hypertension, proteinuria, and hemorrhage in the first 4 weeks of surufatinib treatment. The primary outcome of the study was investigator-assessed progression-free survival (PFS). PFS outcomes were estimated using the Kaplan-Meier method with the log-rank test. Hazard ratios (HRs) were calculated by using univariable and multivariable Cox proportional hazard regression models. Blinded independent image review committee (BIIRC) assessments and 4-week landmark analysis were also performed as supportive evaluations. @@@ Results: During the study period, a total of 242 patients treated with surufatinib were included in the analysis, and 164 (68%) patients had at least one of hypertension, proteinuria, and hemorrhage in the first 4 weeks of treatment. The presence of TRAEs in the first 4 weeks was associated with prolonged median PFS [11.1 versus 9.2 months; HR 0.67, 95% confidence interval (CI) 0.47-0.97; P = 0.036]. In multivariable Cox regression analysis, the presence of TRAEs was also significantly associated with longer PFS (HR 0.65, 95% CI 0.44-0.97; P = 0.035). Similar results were obtained in the BIIRC assessments and 4-week landmark analysis. @@@ Conclusions: Treatment-related hypertension, proteinuria, and hemorrhage could be potential biomarkers to predict antitumor efficacy of surufatinib in patients with advanced NET. Future prospective studies are needed to validate the findings.

• 单位
  山东大学; 中山大学; 复旦大学; 中国医学科学院北京协和医院; 浙江大学; 哈尔滨医科大学; 四川大学; 西安交通大学; 华中科技大学