CTRH as Biomarker of Drug Efficacy: In-Depth Assessment of Real-World Evidence.

Abstract

BACKGROUND Observational studies have suggested that cancer treatment-related hypertension (CTRH) is associated with improved survival and could possibly serve as a biomarker of drug efficacy. Our review aimed to provide an in-depth assessment of the methodological quality of available observational studies. METHODS We systematically searched MEDLINE/PubMed from inception to January 2025 for observational studies that assessed the potential association between the development of CTRH and the risk of cancer-related outcomes, including progression-free survival and overall survival. We assessed the methodological quality of the identified studies using the Risk of Bias in Nonrandomized Studies of Interventions tool. RESULTS We identified 25 observational studies with a total of 6364 patients treated for different cancer types that assessed the potential association between CTRH and the risk of progression-free survival and overall survival. All studies examined CTRH related to the use of vascular endothelial growth factor inhibitors. CTRH was mostly associated with improved progression-free survival and overall survival across cancer types with up to 79% decreased risks. Based on the Risk of Bias in Nonrandomized Studies of Interventions, 8 studies were at critical, 13 studies were at serious, and 4 studies were at moderate risk of bias. Major biases included important residual confounding, reverse causality, immortal time bias, and exposure misclassification. In studies at moderate risk of bias, the survival benefits associated with CTRH disappeared or were attenuated significantly. CONCLUSIONS Observational studies alluding to CTRH being a marker of drug efficacy have major, potentially conclusion-altering biases. Therefore, the findings of our review do not support CTRH as a biomarker of drug efficacy.