Differential Efficacy of Anti-VEGF Antibodies Based on Sex and Race in a Diverse Cohort of Advanced Nonsquamous Non-Small Cell Lung Cancer

Am J Clin Oncol. 2020 Jan;43(1):64-68. doi: 10.1097/COC.0000000000000628.

Abstract

Objectives: Bevacizumab with chemotherapy improved overall survival (OS) in the E4599 trial in metastatic nonsquamous non-small cell lung cancer (NS-NSCLC). A meta-analysis demonstrated an OS benefit with bevacizumab only in a subset of nonwhite patients. We explored the efficacy of antivascular endothelial growth factor antibodies (AVA) in a diverse cohort.

Materials and methods: Patients with advanced (stage IIIB/IV, American Joint Committee Cancer 7th edition) recurrent or metastatic NS-NSCLC diagnosed January 2006 to December 2017 at a single medical center were included. Survival analysis was performed with log-rank testing of the Kaplan-Meier estimator. Univariate models were constructed, and significant variables, age, sex, race were incorporated into a multivariate Cox proportional hazard model. Data analysis was performed on SAS.

Results: A total of 171 patients, 80 were treated with AVA and 91 were untreated. Median age: 63 years, 55% females, 19% non-Hispanic whites, 44% blacks and 32% Hispanic whites; median 40 pack-years of smoking; 11.7% had sensitizing epidermal growth factor receptor mutations. Patients who received AVA had a survival benefit (26.6 vs. 19 mo, P=0.025). Adjusting for age, sex, race/ethnicity, epidermal growth factor receptor mutations, Eastern Cooperative Oncology Group performance status and number of metastases; AVA therapy was associated with improved OS (adjusted hazard ratio=0.62; P=0.049). In a subgroup analysis, females had survival benefit with AVA (median survival: 29.1 vs. 14.2 mo, log-rank P=0.02) which was significant in the adjusted model (adjusted hazard ratio=0.52; P=0.049).

Conclusions: In a diverse cohort of patients with advanced NS-NSCLC, a survival benefit was confirmed with AVA. The greatest magnitude of benefit was in blacks and non-Hispanic whites. A significant survival benefit was limited to female patients.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Racial Groups / statistics & numerical data*
  • Ramucirumab
  • Retrospective Studies
  • Sex Factors
  • Survival Rate
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab