Predictive Value of Circulatory Total VEGF-A and VEGF-A Isoforms for the Efficacy of Anti-PD-1/PD-L1 Antibodies in Patients with Non-Small-Cell Lung Cancer.

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Title:	Predictive Value of Circulatory Total VEGF-A and VEGF-A Isoforms for the Efficacy of Anti-PD-1/PD-L1 Antibodies in Patients with Non-Small-Cell Lung Cancer.
Authors:	Hirakawa, Tetsu¹ (AUTHOR) bgdwj032@yahoo.co.jp, Yamaguchi, Kakuhiro¹ (AUTHOR) ta-masuda@hiroshima-u.ac.jp, Funaishi, Kunihiko¹ (AUTHOR) tnaka@hiroshima-u.ac.jp, Shimoji, Kiyofumi¹ (AUTHOR) nhattori@hiroshima-u.ac.jp, Sakamoto, Shinjiro¹ (AUTHOR), Horimasu, Yasushi¹ (AUTHOR), Masuda, Takeshi¹ (AUTHOR), Nakashima, Taku¹ (AUTHOR), Iwamoto, Hiroshi¹ (AUTHOR), Hamada, Hironobu² (AUTHOR), Yamada, Shingo³ (AUTHOR), Hattori, Noboru¹ (AUTHOR)
Source:	Cancers. Feb2025, Vol. 17 Issue 4, p572. 15p.
Subject Terms:	THERAPEUTIC use of antineoplastic agents, THERAPEUTIC use of monoclonal antibodies, VASCULAR endothelial growth factors, PROTEINS, PROGRAMMED death-ligand 1, LOGISTIC regression analysis, RETROSPECTIVE studies, DESCRIPTIVE statistics, MULTIVARIATE analysis, DRUG efficacy, LUNG cancer, PROGRESSION-free survival, PROPORTIONAL hazards models, EVALUATION
Abstract:	Simple Summary: Vascular endothelial growth factor (VEGF)-A is known to play a crucial role in the tumor microenvironment. This study investigated the relationship between circulating total VEGF-A (tVEGF-A) and its isoforms with the therapeutic effects of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody monotherapy in patients with non-small-cell lung cancer (NSCLC). Higher levels of tVEGF-A were associated with shorter progression-free survival (PFS) in anti-PD-1/PD-L1 antibody monotherapy only when measured in serum, not in plasma. Notably, higher levels of serum VEGF121, an isoform of VEGF-A, were significantly associated with not only shorter PFS but also a lower objective response rate. Serum VEGF121 levels could serve as a useful biomarker for predicting anti-PD-1/PD-L1 antibody monotherapy efficacy in patients with NSCLC. Background/Objectives: Vascular endothelial growth factor (VEGF)-A promotes an immunosuppressive tumor microenvironment, potentially affecting the efficacy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody therapy. VEGF121 and VEGF165, VEGF-A isoforms, promote and inhibit tumor growth, respectively. Additionally, VEGF-A levels differ depending on whether they are measured in serum or plasma. However, whether the serum or plasma levels of total VEGF-A (tVEGF-A) or its isoforms are the most suitable for predicting anti-PD-1/PD-L1 antibody therapy efficacy remains unclear. Methods: Eighty-six patients with non-small-cell lung cancer (NSCLC) who were treated with anti-PD-1/PD-L1 antibody monotherapy between December 2015 and December 2023 were retrospectively enrolled. The association between the serum and plasma levels of tVEGF-A and its isoforms (VEGF121 and VEGF165) and treatment outcomes was analyzed. Results: The median progression-free survival (PFS) was 2.9 months, and the objective response rate (ORR) was 23.3%. PFS was significantly shorter in patients with higher tVEGF-A serum levels (≥484.2 pg/mL) than in those without (median PFS 2.1 vs. 3.7 months, p = 0.004). In contrast, plasma tVEGF-A levels could not be used to stratify PFS. Therefore, the serum levels of VEGF-A isoforms were measured. Patients with higher VEGF121 serum levels (≥523.5 pg/mL) showed both significantly shorter PFS (median PFS 2.3 vs. 3.3 months, p = 0.022) and a lower ORR (9.7% vs. 30.9%, p = 0.033) than those without. Multivariate Cox and logistic regression analyses showed that higher levels of serum VEGF121 were significantly associated with shorter PFS and a lower ORR. Conclusions: Serum VEGF121 levels may be useful in predicting anti-PD-1/PD-L1 antibody monotherapy efficacy. [ABSTRACT FROM AUTHOR]
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ISSN:	20726694
DOI:	10.3390/cancers17040572
Published in:	Cancers
Language:	English