Bevacizumab Enhances Pathological Complete Response and Survival When Added to Neoadjuvant Chemoradiotherapy in Pd-L1-Negative Tumor Microenvironment of Locally Advanced Rectal Cancer
Journal
SSRN
ISSN
15565068
Date Issued
2025
Author(s)
Chiang, Yun
Tsai, Chao-Ling
Shun, Chia-Tung
Chen, Yu-Hsuan
Chen, Tzo-Chun
Tsai, Cheng-Hong
Cheng, Jason Chia-Hsien
Abstract
Background This study investigated the impact of adding bevacizumab to neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC), and explored predictive biomarkers of pathological response. Methods Patients with LARC who underwent NCRT with or without bevacizumab, followed by curative resection from 2009 to 2021 were evaluated. Associations between clinical factors and pathological complete remission (pCR), overall survival (OS), and progression-free survival (PFS) were analyzed using ANOVA and the Cox proportional hazards model. NanoString analysis of pre-treatment tumor specimens was used to identify potential predictive biomarkers, which were validated via immunohistochemistry (IHC). Results Among 200 patients, 39 achieved pCR (18/54 with bevacizumab vs. 21/146 without, p = 0.004). With a median follow-up of 117 months, 5-year OS and PFS rates were 86.4% and 76.0%, respectively. Multivariate analysis identified clinical N0 disease and bevacizumab as independent predictors of pCR, which, in turn, was the only independent factor associated with improved OS (HR=0.097, p=0.021) and PFS (HR=0.17, p=0.016). NanoString analysis revealed increased macrophages, exhausted CD8 T cells, and activated signaling pathways linked to programmed death-ligand 1 (PD-L1) production in the bevacizumab group. IHC analysis demonstrated significantly higher PD-L1 positivity in immune cell (IC) among non-pCR patients in the bevacizumab group (p=0.031), but not in the non-bevacizumab group (p=0.075). Conclusions Adding bevacizumab to NCRT in LARC patients improves survival by increasing pCR rate with tolerable toxicities. PD-L1 positivity in IC may predict poorer response to bevacizumab. © 2025, The Authors. All rights reserved.
Subjects
Bevacizumab
Neoadjuvant chemoradiotherapy
Pathological complete remission
PD-L1
rectal cancer
Publisher
Elsevier BV
Type
other