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

Abstract

Introduction Pre-clinical 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) is associated with improved overall survival in patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC). 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 one of four 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. Overall survival (OS) was measured from the initiation of chemotherapy until death, disenrollment, or December 31, 2012. Results Of the 1,465 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 overall survival (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 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% confidence interval (CI), 0.61–0.88), for CP patients and 0.79 (95% CI, 0.51–1.21) for CPB patients. Conclusions Concomitant ASI receipt during CP or CPB therapy for NS-NSCLC was associated with improved survival, though the association was only statistically significant in the CP group.

Targeting the renin-angiotensin system to improve cancer treatment: Implications for immunotherapy

“…The use of RASi was associated with better outcomes in patients with different solid tumors who received platinum-based CHT ( 142 , 143 , 149 , 165 , 172 ). The gain in overall survival (OS; the length of time from either the date of diagnosis or the start of treatment that patients are still alive) ranged from ~3 months in advanced non–small cell lung cancer (NSCLC) to 5.7 months in advanced gastric cancer and even 11 months in metastatic colorectal cancer (CRC) ( 142 , 149 , 165 , 172 ). In line with the clinical data, experimental studies showed that platinum-based CHT can increase VEGF production through up-regulation of AT1R expression.…”

“…In addition, RASi use was effective in both early and advanced tumor stages. In some tumor types, the effect of RASi was investigated primarily in either early tumors (such as resected urinary tract cancer) ( 130 , 147 , 150 , 151 ) or advanced stages (such as metastatic NSCLC) ( 142 , 149 ). In RCC and CRC, positive outcomes were reported for both early ( 144 , 167 ) and metastatic diseases ( 137 – 140 , 172 ).…”

Paths for Improving Bevacizumab Available in 2018: The ADZT Regimen for Better Glioblastoma Treatment

“…Also in 2017, Menter et al found similar but slightly different results in nonsquamous, non-small cell lung cancer treated with carboplatin and paclitaxel with or without bevacizumab. Bevacizumab prolonged survival, as did an ACEi or ARB, but increased survival by addition of an ACE inhibitor/ARB to bevacizumab did not reach statistical significance for additive effect [74].…”

Liver Protective Effects of Renin-Angiotensin System Inhibition Have No Survival Benefits in Hepatocellular Carcinoma Induced By Repetitive Administration of Diethylnitrosamine in Mice

“…Furthermore, other studies revealed that ACEIs or ARBs might decrease the risk of esophageal [ 16 ] and keratinocyte [ 17 ] carcinoma. Their use was also associated with increased response in rectal cancer [ 18 ] and longer OS in patients with renal cell, pancreatic, brain, and lung cancer [ 19 ] [ 20 ]. However, little is known about the impact of RAS inhibition on the OS of HCC on the experimental and clinical sides.…”