Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20.
OBJECTIVE
This double-blind randomized phase II trial examined whether vandetanib, an inhibitor of vascular endothelial and epidermal growth factor receptors, could prolong progression-free survival in responding patients with small-cell lung cancer.


METHODS
Eligible patients with complete response (CR) or partial response (PR) to combination chemotherapy (+/- thoracic or prophylactic cranial radiation) received oral vandetanib 300 mg/d or matched placebo. With 100 patients and 77 events, the study had 80% power to detect an improvement in median progression-free survival from 4 to 6.5 months (one-sided, 10%-level test).


RESULTS
Between May 2003 and March 2006, 107 patients were accrued; 46 had limited disease and 61 extensive disease. There were fewer patients with a performance status of 0 (n = 11 v 20), and fewer had CR to initial therapy (n = 4 v 8) in the vandetanib arm. Vandetanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash. Asymptomatic Corrected QT interval (QTC) prolongation was observed in eight vandetanib patients. Median progression-free survival for vandetanib and placebo was 2.7 and 2.8 months, respectively (hazard ratio [HR], 1.01; 80% CI, 0.75 to 1.36; one-sided P = .51). Overall survival for vandetanib was 10.6 versus 11.9 months for placebo (HR, 1.43; 80% CI, 1.00 to 2.05; one-sided P = 0.9). In planned subgroup analyses, a significant interaction was noted (P = .01): limited-stage vandetanib patients had longer overall survival (HR, 0.45; one-sided P = .07) and extensive-stage vandetanib patients shorter survival compared with placebo (HR, 2.27; one-sided P = .996).


CONCLUSIONS
Vandetanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer.
Arnold
Andrew M
AM
National Cancer Institute of Canada-Clinical Trials Group, Kingston, Ontario, Canada.
Seymour
Lesley
L
Smylie
Michael
M
Ding
Keyue
K
Ung
Yee
Y
Findlay
Brian
B
Lee
Christopher W
CW
Djurfeldt
Marina
M
Whitehead
Marlo
M
Ellis
Peter
P
Goss
Glenwood
G
Chan
Adrien
A
Meharchand
Jacinta
J
Alam
Yasmin
Y
Gregg
Richard
R
Butts
Charles
C
Langmuir
Peter
P
Shepherd
Frances
F
D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D010919:Placebos; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage*; D016896:Treatment Outcome
D010880:Piperidines; D010919:Placebos; D011799:Quinazolines; C452423:vandetanib