Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study

Medicine (Baltimore). 2021 Sep 3;100(35):e27130. doi: 10.1097/MD.0000000000027130.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Bevacizumab / therapeutic use*
  • China / epidemiology
  • Female
  • Genes, erbB-1*
  • Genes, erbB-2*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Pharmacogenomic Variants
  • Progression-Free Survival
  • Proportional Hazards Models
  • Proto-Oncogene Mas
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / metabolism


  • Antineoplastic Agents, Immunological
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor