APATINIB-INDUCED HYPERTENSION ASSOCIATED WITH BETTER PROGNOSIS IN PATIENT WITH SOLID TUMOR

Objective: To investigate the incidence of apatinib-induced hypertension (HTN) in the treatment of patients with solid tumor in real world and to determine whether apatinib-induced HTN is associated with its anti-tumor efficacy. Design and method: We retrospectively collected the medical records of patients with solid tumor treated with apatinib in Lanzhou University Second Hospital and Gansu Provincial Cancer Hospital, from Oct 1st 2014 to Jun 30st 2019. The patients were then prospectively followed to determine the disease state, time of disease progression and death, as well as whether or not have newly initiated HTN. The mean follow-up was 16.5month, with the longest follow-up of 48 months. The apatinib-induced HTN was defined as either newly initiated HTN in patients with normal blood pressure or increases of antihypertensive intensity in patients with pre-existed HTN. The prognosis of patients was estimated with progression-free survival (PFS) and overall survival (OS). Results: A total of 400 patients were enrolled, of whom 136 (34%) were diagnosed with HTN induced by apatinib. The primary tumor in 40% of the patients were gastrointestinal cancer, followed by hepatobiliary cancer (14.5%) and lung cancer (13.3%). Patients in HTN group were older (p = 0.03), more frequently with proteinuria (p = 0.035) and higher dosage of apatinib (p = 0.024). The survival analysis showed that apatinib-induced HTN was associated with significantly longer PFS, as well as OS (both p < 0.01), the differences existed both in univariate and multivariate analyses. The subgroup analyses were performed in patients with gastrointestinal cancer, hepatobiliary cancer, and lung cancer, all showed consistent results. Conclusions: HTN is one of the most common side effects of apatinib in the treatment of solid tumors, with an incidence of as high as 34% in real world. Apatinib-induced HTN is significantly associated with better anti-tumor efficacy in patients with solid tumors. Given that there is still no effective predictive biomarker for apatinib, drug-induced HTN may be used as an surrogate one. The development of new antihypertensive drugs with better antihypertensive effects while no influences on antitumor activity, is in urgent need.