Effect of Angiotensin System Inhibitors on Survival in Patients Receiving Chemotherapy for Advanced Non-Small-Cell Lung Cancer

Clin Lung Cancer. 2017 Mar;18(2):189-197.e3. doi: 10.1016/j.cllc.2016.07.008. Epub 2016 Aug 20.


Introduction: Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with improved overall survival (OS) in patients with advanced nonsquamous, non-small-cell lung cancer (NS-NSCLC).

Patients and methods: In a retrospective cohort study, adult patients diagnosed with stage IIIB or IV NS-NSCLC between 2005 and 2011 were identified from tumor registries at 1 of 4 Kaiser Permanente regions. Survival differences between those who did and did not receive ASIs concomitant with chemotherapy (CP or CPB) were assessed using propensity score-matched proportional hazard models. OS was measured from the initiation of chemotherapy until death, disenrollment, or December 31, 2012.

Results: Of the 1465 CP and 348 CPB patients included, 273 (19%) and 78 (22%), respectively, received concomitant ASI. For CP patients with and without concomitant ASI exposure, median OS was 12.0 and 8.4 months, respectively (crude hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.84). For CPB patients, the comparable median OS was 14.9 and 11.9 months, respectively (crude HR, 0.77; 95% CI, 0.57-1.02). Using propensity score-matched cohorts, the HR for concomitant ASI use was 0.73 (95% CI, 0.61-0.88) for CP patients and 0.79 (95% CI, 0.51-1.21) for CPB patients.

Conclusion: Concomitant ASI receipt during CP or CPB therapy for NS-NSCLC was associated with improved survival, although the association was only statistically significant in the CP group.

Keywords: Angiotensin; Bevacizumab; Chemotherapy; Microenvironment; Non–small-cell lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Paclitaxel / administration & dosage
  • Prognosis
  • Renin-Angiotensin System / drug effects*
  • Retrospective Studies
  • Survival Rate


  • Bevacizumab
  • Carboplatin
  • Paclitaxel