Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study
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ABSTRACT: Bevacizumab (BV) plus chemotherapy is broadly used in advanced ovarian cancer (OC). However, the efficacy of BV-based regimens for advanced OC patients is not satisfactory. Therefore, it is urgent to explore the predictive genetic biomarkers for BV.Tumor tissues from advanced OC patients receiving BV-based regimens were analyzed with a 150-gene targeted panel for next generation sequencing. The associations between gene alterations or clinicopathology features and progression-free survival (PFS) were analyzed by Kaplan-Meier curves or Cox regression. The association of the genetic alteration in potential predictive genes and expressions of 11 vascular endothelial growth factor-related genes were analyzed in The Cancer Genome Atlas cohort using 292 OC cases.Sixty two Chinese advanced OC patients treated with BV-based therapy were included. The median PFS of was 6.9 months, and objective response rate was 14.5%. In multivariate Cox regression analysis, the status of endothelial growth factor receptor (EGFR) (hazard ratio = 6.39, 95% confidence interval [CI] 2.25-18.13, P < .001) and human epidermal growth factor receptor 2 (HER2) (hazard ratio = 3.58, 95% CI 1.27-10.08, P = .016) were significantly correlated with PFS. MYC Proto-Oncogene amplification seemed to have a positive trend (hazard ratio = 0.21, 95% CI 0.05-1.02, P = .052). Moreover, EGFR and HER2 alterations were not prognostic factors of overall survival for OC in The Cancer Genome Atlas OC cohort. The vascular endothelial growth factor-related signature analysis indicated vascular endothelial factor A expression was upregulated with EGFR alterations (P = .034) which may be involved in BV resistance, and HER2 alterations were associated with hypoxia inducible factor 1 subunit alpha overexpression significantly (P = .029).EGFR or HER2 alterations are negative predictors of PFS for OC patient treated with BV plus chemotherapy. Therefore, the clinicians may consider to use alternative regimens such as anti-EGFR or anti-HER2 targeted therapy instead of BV-based regimens on these patients when standard care fail.
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Unlike for PARP inhibitors, there are no clinically approved biomarkers to predict responses of women with ovarian cancer to the anti-angiogenic bevacizumab.
“Unlike for PARPis, there are no clinically approved biomarkers to predict responses of women with ovarian cancer to the anti-angiogenic bevacizumab, although numerous studies have focused on this area (Buechel et al., 2021; Gao et al., 2021; Hsu et al., 2021).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Gao et al., 2021
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“Finally, amplification of the EGFR gene is also associated with more aggressive tumors (i.e., more invasive and metastatic tumors), and studies have shown that EOC patients with amplification of EGFR have a poorer response to chemotherapy and shorter PFS than other patients with EOC [55,56].”
- Authors
- Gao, J., Li, F., Liu, Z., Huang, M., Chen, H., Liao, G., Meng, J., Wang, Q., Zhao, H., Li, C., Ji, J., Cai, S., & Du, N.
- Affiliations
- Chinese PLA General Hospital (CN)
- 3D Medicines, Inc. (China) (CN)
- Department of Oncology, Chinese PLA Rocket General Hospital, China
- Bethune International Peace Hospital (CN)
- The Medical Department, 3D Medicines Inc., Shanghai, China
- Corresponding author
- Du, Nan
- ORCID
- Venue
- Medicine
- Published
- 2021-09-03
- Volume
- 100
- Issue
- 35
- Pages
- e27130
- ISSN
- 0025-7974 (ISSN-L)
- 1536-5964
- PMC
- PMC8415939
- OpenAlex
- W3197410476
- Cited by
- 6
- References
- 36
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 2
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Beijing Science and Technology Planning Project (Z171100000417011)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- advanced ovarian cancer, bevacizumab, progression-free survival, predictive biomarkers, EGFR alterations, HER2 alterations, MYC amplification, vascular endothelial growth factor, VEGF-A, HIF1A, anti-VEGF therapy resistance, targeted therapy
- MeSH terms
- Bevacizumab, Pharmacogenomic Variants, Antineoplastic Agents, Immunological, Progression-Free Survival, Proto-Oncogene Mas, Adult, Aged, Aged, 80 and over, China, Female, Humans, Middle Aged, Ovarian Neoplasms, Retrospective Studies, Proportional Hazards Models, Genes, erbB-2, Genes, erbB-1, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A, Hypoxia-Inducible Factor 1, alpha Subunit
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