Yong Zhou,* Zhengcheng Liu,* Ao Yu, Gefei Zhao, Baojun Chen

Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Baojun Chen, Email cbaoj_608@126.com

Abstract: In recent years, the combination of immune checkpoint inhibitors (ICIs) with antiangiogenic agents has led to significant breakthroughs in cancer treatment. Such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Antiangiogenic therapy plays a pivotal role in normalizing blood vessels and remodeling the tumor immune microenvironment while ICIs not only enhance the host’s antitumor immune response by blocking negative regulatory signals but also promote vascular normalization. The communication between the vasculature and immune system enables the combined use of ICIs and antiangiogenic therapy to have a synergistic effect. Clinical research has also demonstrated that this combination therapy can significantly improve the efficacy and survival of patients with various solid tumors, the addition of pembrolizumab to axitinib can significantly improve PFS (15.4 m vs 11.1 m) compared to sunitinib in first-line treatments of advanced renal cell carcinoma (RCC). Bevacizumab is the first approved anti-VEGF monoclonal antibody. Bevacizumab in combination with atezolizumab obtain significant benefit in terms of PFS (6.9 m vs 4.3 m) compared to sorafenib in advanced hepatocellular carcinoma (HCC). In addition, a series of investigations have been conducted in other solid tumors, such as colorectal cancer (CRC). Future research directions include the development of novel antiangiogenic agents and ICIs, the exploration of other combination strategies (eg, with chemotherapy or targeted therapy), and the identification of biomarkers for patient selection and monitoring response to therapy. Additionally, more studies are needed to understand the optimal timing and sequencing of these therapies to maximize patient benefit. This review aims to elucidate the mechanisms of action of ICIs plus antiangiogenic drugs and provide summaries of related clinical trials. Meanwhile, we outline the current challenges faced and future directions, include the identification of biomarkers for patient selection and monitoring response to therapy, particularly highlighting the newer therapy strategies.

Keywords: immune checkpoint inhibitors, antiangiogenic agents, combination regimen, solid tumors