Association between tyrosine-kinase inhibitor induced hypertension and treatment outcomes in metastatic renal cancer

Background Tyrosine-kinase inhibitor (TKI) drugs have been considered first line treatment for metastatic renal cell cancer (RCC) for over a decade. TKI-induced hypertension is a common adverse-event in patients treated for metastatic RCC. Aim This study was aimed at investigating an association between TKI-induced hypertension and treatment outcomes for metastatic RCC patients. Methods and results Retrospective data pertaining to patients with histologically or radiologically confirmed metastatic RCC treated with sunitinib, pazopanib, sorafenib, axitinib or cabozantinib between June 2012 and May 2019 were evaluated. Clinical information and serial blood pressure measurements were extracted from medical records for each patient. We compared objective response rate, progression-free survival (PFS), and 12-month survival between TKI-induced hypertension (TIH) and non-TIH groups using chi(2)and Mann-Whitney tests. Out of 72 patients screened, 52 met study eligibility criteria. The median age at diagnosis was 61 years (range: 42-85 years) with a clear male predominance. The majority of patients had a history of nephrectomy with clear cell pathology. Almost all patients were on first-line TKI therapy with sunitinib or pazopanib. Median follow-up was 11 months. About half of patients developed TKI-induced hypertension (grade 2-3). In the TIH group 82% were commenced on an antihypertensive agent. Median PFS measured 30.5 weeks for TIH group compared to 22.2 weeks for non-TIH (P= .05). The 6 month and 12 month survival rates for TIH were 82% and 56%, respectively, as compared to 76% and 44% for non-TIH. Conclusion The occurrence of TKI-induced hypertension was found to be a positive prognostic factor for progression in patients with metastatic RCC.