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, Isamu Okamoto
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. This prospective study conducted in a phase 3 trial has shown that pre-treatment serum VEGF-A was a negative biomarker for PFS in patients with advanced NSCLC treated with a combination of an anti-angiogenic agent and a PD-1 axis inhibitor.