Abstract | 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: TRIAL REGISTRATION: ClinicalTrials.govNCT02589821; https://clinicaltrials.gov/ct2/show/NCT02589821 and ClinicalTrials.gov NCT02588170; https://clinicaltrials.gov/ct2/show/NCT02588170.
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Authors | J Li, Y Cheng, C Bai, J Xu, L Shen, J Li, Z Zhou, Z Li, Y Chi, X Yu, E Li, N Xu, T Liu, W Lou, Y Bai, X Yuan, X Wang, Y Yuan, J Chen, S Guan, S Fan, W Su |
Journal | ESMO open
(ESMO Open)
Vol. 7
Issue 2
Pg. 100453
(04 2022)
ISSN: 2059-7029 [Electronic] England |
PMID | 35344750
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. |
Chemical References |
- Biomarkers
- Indoles
- Pyrimidines
- Sulfonamides
- surufatinib
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Topics |
- Biomarkers
- Female
- Humans
- Hypertension
- Indoles
- Male
- Neuroendocrine Tumors
(drug therapy, pathology)
- Proteinuria
- Pyrimidines
- Sulfonamides
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