Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC Clinical Trials Group Study BR24.
BACKGROUND
Hypertension (HTN), a recognized adverse effect of angiogenesis inhibitors, may be a potential biomarker of activity of these agents. We conducted a retrospective analysis to examine the incidence and predictors of the development of on-treatment HTN with the vascular endothelial growth factor receptor tyrosine kinase inhibitor cediranib, and the relationship of this adverse event with treatment outcomes.


METHODS
BR24 was a double-blind placebo-controlled phase II trial of carboplatin/paclitaxel chemotherapy with either daily oral cediranib or placebo in patients (n = 296) with advanced non-small-cell lung cancer (NSCLC). Exploratory analyses characterized relationships between HTN, baseline variables, and efficacy outcomes.


RESULTS
New onset or worsening of preexisting HTN (treatment-emergent HTN) was more frequent in patients receiving cediranib (68 versus 45%, P < 0.0001). Factors associated with HTN in all randomized patients were good performance status and treatment with cediranib. In both arms, treatment-emergent HTN was associated with improved efficacy outcomes, but there was no evidence of a differential treatment effect, with nonsignificant interaction P values.


CONCLUSIONS
In advanced NSCLC, HTN is frequent in patients receiving chemotherapy, with or without cediranib. The development of HTN was favorably prognostic in these patients, but not predictive of a differential outcome with cediranib.
Goodwin
R
R
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Ding
K
K
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Seymour
L
L
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
LeMaître
A
A
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Arnold
A
A
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Shepherd
F A
FA
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Dediu
M
M
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Ciuleanu
T
T
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Fenton
D
D
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Zukin
M
M
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Walde
D
D
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Laberge
F
F
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Vincent
M
M
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Ellis
P M
PM
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Laurie
S A
SA
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada. Electronic address: slaurie@ottawahospital.on.ca.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D010919:Placebos; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D007211:Indoles
D016190:Carboplatin; D017239:Paclitaxel; D010919:Placebos; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; C500926:cediranib; D007211:Indoles