Association between fruquintinib-induced hypertension and clinical outcomes from FRUTIGA, a phase III study of fruquintinib plus paclitaxel in previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma

BackgroundHypertension is a common adverse drug reaction of using angiogenesis inhibitors targeting the vascular endothelial growth factor pathway, such as bevacizumab or ramucirumab. Moreover, angiogenesis inhibitor-induced hypertension is associated with improved clinical outcomes in various cancers. Here, we retrospectively analyzed these data from FRUTIGA to evaluate whether clinical outcomes were associated with fruquintinib-induced hypertension in advanced G/GEJ adenocarcinoma patients treated with fruquintinib plus paclitaxel.MethodsFRUTIGA was a randomized, double-blind, placebo-controlled phase 3 study. The treatment arm was given fruquintinib 4 mg orally, once daily for 3 weeks followed by 1 week off, plus paclitaxel 80 mg/m2 intravenously on days 1/8/15 per cycle. Post hoc analyses were conducted in the treatment arm.Results351 patients were randomized to fruquintinib plus paclitaxel treatment arm. Among these patients, 59 (16.8%) experienced fruquintinib-induced hypertension. 23 (6.6%) experienced grade 3 or more fruquintinib-induced hypertension. No patient permanently discontinued due to hypertension. These patients had a better clinical outcome than those with no occurrence of fruquintinib-induced hypertension, with higher objective response rates (ORR) of 57.6% (95% CI 44.1%-70.4%) versus 39.4% (95% CI 33.7%-45.2%) (p=0.0136). Progression-free survival (PFS) and overall survival (OS) were 8.08 months (95% CI 6.4-8.3) (p=0.0003) and 11.80 months (95% CI 9.3-16.2) (p=0.0157) in the fruquintinib-induced hypertension group, versus 4.63 months (95% CI 4.6-5.9) and 9.36 months (95% CI 8.4-10.4) in no fruquintinib-induced hypertension group, respectively.ConclusionsFruquintinib-induced hypertension was associated with higher ORR, longer PFS and OS in advanced G/GEJ adenocarcinoma patients. The fruquintinib-induced hypertension could potentially be predictive of clinical outcomes for pts with treatment with fruquintinib plus paclitaxel.Clinical trial identificationNCT03223376.Legal entity responsible for the studyHutchmed Limited.FundingThe National Science and Technology Major Project (project no. 2019ZX09301012), the Science and Technology Commission of Shanghai Municipality (Science, Technology and Innovation Action Plan, project no. 17431900100) and Hutchmed Limited.DisclosureQ. Liu, S. Fan: Financial Interests, Personal, Full or part-time Employment: Hutchmed Limited. All other authors have declared no conflicts of interest.