Serum VEGF-A as a biomarker for the addition of bevacizumab to chemo-immunotherapy in metastatic NSCLC

Kentaro Tanaka (), Jun Sugisaka, Yoshimasa Shiraishi, Yasutaka Watanabe, Haruko Daga, Koichi Azuma, Kazumi Nishino, Masahide Mori, Takayo Ota, Haruhiro Saito, Akito Hata, Tadashi Sakaguchi, Toshiyuki Kozuki, Hiroaki Akamatsu, Hirotaka Matsumoto, Motoko Tachihara, Kazushige Wakuda, Yuki Sato, Tomohiro Ozaki, Yuko Tsuchiya-Kawano, Nobuyuki Yamamoto, Kazuhiko Nakagawa and Isamu Okamoto
Additional contact information
Kentaro Tanaka: Kyushu University
Jun Sugisaka: Sendai Kousei Hospital
Yoshimasa Shiraishi: Kyushu University
Yasutaka Watanabe: Saitama Cancer Center
Haruko Daga: Osaka City General Hospital
Koichi Azuma: Kurume University School of Medicine
Kazumi Nishino: Osaka International Cancer Institute
Masahide Mori: NHO Osaka Toneyama Medical Center
Takayo Ota: Izumi City General Hospital
Haruhiro Saito: Kanagawa Cancer Center
Akito Hata: Kobe Minimally Invasive Cancer Center
Tadashi Sakaguchi: Matsusaka Municipal Hospital
Toshiyuki Kozuki: NHO Shikoku Cancer Center
Hiroaki Akamatsu: Wakayama Medical University
Hirotaka Matsumoto: Hyogo Prefectural Amagasaki General Medical Center
Motoko Tachihara: Kobe University Graduate School of Medicine
Kazushige Wakuda: Shizuoka Cancer Center Hospital
Yuki Sato: Kobe City Medical Center General Hospital
Tomohiro Ozaki: Kishiwada City Hospital
Yuko Tsuchiya-Kawano: Kitakyushu Municipal Medical Center
Nobuyuki Yamamoto: NHO Shikoku Cancer Center
Kazuhiko Nakagawa: Kindai University Faculty of Medicine
Isamu Okamoto: Kyushu University

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Anti-vascular endothelial growth factor (VEGF) agents in combination with immunotherapies have improved outcomes for cancer patients, but predictive biomarkers have not been elucidated. We report here a preplanned analysis in the previously reported APPLE study, a phase 3 trial evaluating the efficacy of the bevacizumab in combination with atezolizumab, plus platinum chemotherapy in metastatic, nonsquamous non-small cell lung cancer (NSCLC). We investigated the correlation of serum VEGF-A and its isoforms at baseline with treatment response by using an enzyme-linked immunosorbent assay. We reveal that the addition of bevacizumab significantly improves the progression-free survival in patients with the low VEGF-A level. Our results demonstrate that measuring serum VEGF-A or its isoforms may identify NSCLC patients who are likely to benefit from the addition of bevacizumab to immunotherapy. These assays are easy to measure and have significant potential for further clinical development.

Date: 2025
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DOI: 10.1038/s41467-025-58186-7

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