Serum VEGF-A as a biomarker for the addition of bevacizumab to chemo-immunotherapy in metastatic NSCLC
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.
Authors
- Yoshimasa Shiraishi (ORCID: https://orcid.org/0000-0001-5015-193X)
- Jun Sugisaka (ORCID: https://orcid.org/0000-0002-1000-0077)
- Takayo Ota (ORCID: https://orcid.org/0000-0003-1630-8301)
- Kazumi Nishino (ORCID: https://orcid.org/0000-0003-2000-7472)
- Tadashi Sakaguchi (ORCID: https://orcid.org/0000-0003-1103-4276)
- Kazushige Wakuda (ORCID: https://orcid.org/0000-0002-6369-2388)
- Haruhiro Saito (ORCID: https://orcid.org/0000-0002-8541-8339)
- Motoko Tachihara
- Koichi Azuma (ORCID: https://orcid.org/0000-0001-5040-5856)
- Yuko Tsuchiya‐Kawano
- Hirotaka Matsumoto (ORCID: https://orcid.org/0000-0003-4538-6456)
- Tomohiro Ozaki
- Isamu Okamoto (ORCID: https://orcid.org/0000-0002-7587-6096)
- Yuki Sato (ORCID: https://orcid.org/0000-0002-7829-7524)
- Toshiyuki Kozuki (ORCID: https://orcid.org/0000-0001-8432-8975)
- Haruko Daga (ORCID: https://orcid.org/0000-0002-5191-6233)
- Hiroaki Akamatsu (ORCID: https://orcid.org/0000-0001-5856-5512)
- Nobuyuki Yamamoto (ORCID: https://orcid.org/0000-0002-1006-7394)
- Kazuhiko Nakagawa (ORCID: https://orcid.org/0000-0003-1284-9776)
- Kentaro Tanaka (ORCID: https://orcid.org/0000-0003-4602-4465)
- Akito Hata (ORCID: https://orcid.org/0000-0001-7035-7249)
- Masahide Mori (ORCID: https://orcid.org/0009-0007-9223-3854)
- Yasutaka Watanabe (ORCID: https://orcid.org/0000-0002-3679-4864)
Institutions
- Kurume University (JP)
- Kagoshima University (JP)
- Kyushu University (JP)
- Wakayama Medical University (JP)
- Kanagawa Prefectural Hospital Organization (JP)
- Shizuoka Cancer Center (JP)
- Osaka City General Hospital (JP)
- Toneyama National Hospital (JP)
- Kishiwada City Hospital (JP)
- Saitama Cancer Center (JP)
- Kitakyushu Municipal Medical Center (JP)
- Izumi City General Hospital (JP)
- Hyogo Prefectural Amagasaki General Medical Center (JP)
- Shikoku Cancer Center (JP)
- Osaka International Cancer Institute (JP)
- Soka Municipal Hospital (JP)
- Kobe City Medical Center General Hospital (JP)
- Sendai Kousei Hospital (JP)
- Kanagawa Cancer Center
- Kobe University (JP)
- Kindai University (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-22
- DOI
- https://doi.org/10.1038/s41467-025-58186-7
- Citations
- 14
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 14.64