Correlation between Efficacy and Cardiovascular Adverse Events in Patients with Advanced Solid Cancer Who Received VEGF Pathway Inhibitors - Hypertension within the First Eight Weeks Is Associated with Favorable Outcomes

Sep 21, 2026

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VEGF pathway inhibitors are widely used for advanced cancers, yet cardiovascular adverse events (CVAEs) such as hypertension, heart failure, arrhythmia, thromboembolism, and hemorrhage limit optimal management. Using real-world data, this study assessed CVAE frequency and severity in patients receiving ramucirumab, regorafenib, pazopanib, sunitinib, or sorafenib, and tested associations between CVAEs and treatment efficacy. Early or overall CVAEs were common, and higher-grade CVAEs related to more favorable progression-free survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Abstract

Objective

Methods

Results

Conclusion

Introduction

VEGF signaling and cancer progression

VEGF pathway inhibitors and known cardiovascular toxicities

Prior evidence on efficacy–CVAEs correlation

doi: 10.2169/internalmedicine.3373-23 Intern Med 64: 177-185, 2025 [http://internmed.jp](http://internmed.jp) 【ORIGINAL ARTICLE】 Correlation between Efficacy and Cardiovascular Adverse Events in Patients with Advanced Solid Cancer Who Received VEGF Pathway Inhibitors: Hypertension within the First Eight Weeks Is Associated with Favorable Outcomes of Patients Treated with VEGF Pathway Inhibitors Yuya Yoshida 1,2, Masanobu Takahashi 1,2, Keigo Komine 2, Sakura Taniguchi 2, Hideharu Yamada 2, Keiju Sasaki 2, Sho Umegaki 2, Yoshifumi Kawamura 2, Yuki Kasahara 2,3, Kota Ouchi 2, Hiroo Imai 2, Ken Saijo 2, Hidekazu Shirota 2, Noriko Takenaga 2 and Chikashi Ishioka 1,2 Abstract: Objective Many vascular endothelial growth factor (VEGF) pathway inhibitors are used in the treatment of patients with various advanced cancers; however, treatments induce cardiovascular adverse events (CVAEs), such as hypertension, heart failure, arrhythmia, arterial or venous embolism, and hemorrhage. Some studies have suggested a correlation between efficacy and CVAEs; however, further evidence is required. This study evaluated real-world data concerning the frequency and degree of CVAEs and possible associations between CVAEs and efficacy in such patients. Methods We analyzed CVAEs observed in 294 patients with advanced cancer who were treated with ramucirumab, regorafenib, pazopanib, sunitinib, or sorafenib. Results CVAEs of any grade and proteinuria within 8 weeks after the initiation of VEGF pathway inhibitors (early) or during the treatment period (total period) were observed in 72-85% and 77-92% of the patients, respectively. The progression-free survival (PFS) of patients with a CVAE of grade 􀀂 1 in the early period was favorable compared with the PFS of those who had no CVAE (median, 4.9 vs. 3.5 months, p=0.016, log-rank test) . Furthermore, the PFS of patients with a CVAE grade 􀀂 3 in the early period was favorable compared to that of those with CVAEs of grades 0-2 . Taken together, a higher degree of CVAE was correlated with favorable patient outcomes. Conclusion This study revealed the frequency and degree of CVAEs in patients with solid cancers who received VEGF pathway inhibitors in a real-world setting and added evidence regarding the correlation between CVAEs and efficacy of VEGF pathway inhibitors. Key words: VEGF pathway inhibitors, cardiovascular adverse events, hypertension (Intern Med 64: 177-185, 2025) (DOI: 10.2169/internalmedicine.3373-23) 1 Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Japan, 2 Department of Medical Oncology, Tohoku University Hospital, Japan and 3 Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Japan Received: December 21, 2023; Accepted: April 10, 2024; Advance Publication by J-STAGE: June 13, 2024 Correspondence to Dr. Masanobu Takahashi, [masanobu.takahashi.a7@tohoku.ac.jp](masanobu.takahashi.a7@tohoku.ac.jp) Introduction Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis around tumor cells and is necessary for tumor progression in various cancers (1, 2) . VEGF secreted by tumors and the surrounding stroma stimulates the proliferation of endothelial cells, which promotes the formation of new blood vessels (2) . Targeting VEGF and its receptors (VEGFRs) has been a promising therapeutic approach in various cancers, such as colorectal cancer, non-small-cell lung cancer, renal cell carcinoma, breast cancer, ovarian can cer, gastric cancer, hepatocellular carcinoma, cervical cancer, glioblastoma multiforme, neuroendocrine tumor, and soft tissue sarcoma. Bevacizumab was first approved by the US Food and Drug Administration in 2004 (2) . Thereafter, many antibodies, such as ramucirumab and ziv-aflibercept, and smallmolecule inhibitors, such as sorafenib, sunitinib, and pazopanib, which target VEGF or VEGFRs, have been applied in daily clinical practice for the treatment

FAQs

What clinical question does this study address about VEGF pathway inhibitors?

It evaluates how often and how severe cardiovascular adverse events (CVAEs) are in real-world patients and whether CVAEs are associated with treatment efficacy.

Which drugs were analyzed, and how many patients were included?

The analysis included 294 patients treated with ramucirumab, regorafenib, pazopanib, sunitinib, or sorafenib.

How were CVAEs related to patient outcomes in terms of progression-free survival?

In the early period, patients with CVAE grade ≥1 and ≥3 showed favorable progression-free survival compared with those without CVAEs or with lower-grade CVAEs.

Sep 21, 2026

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