A randomized, phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy.
BACKGROUND
This randomized, phase II study investigated whether benefit could be obtained by giving vandetanib, an oral inhibitor of vascular endothelial and epithelial growth factor receptor, as a maintenance treatment in non-small cell lung cancer (NSCLC).


METHODS
Patients were randomly assigned to either vandetanib or placebo after completion of 4 cycles of first-line chemotherapy. A progression-free survival (PFS) rate at 3 months was selected as the primary endpoint. We set a maximum PFS rate at 3 months to 30% (null hypothesis), and a minimum PFS rate at 3 months to 50% (alternative hypothesis).


RESULTS
At the interim analysis, 9 of 24 patients in the vandetanib arm were progression-free at 3 months, whereas 7 of 24 in the placebo arm were progression-free. The placebo arm was closed at the first stage. The vandetanib arm proceeded to the second stage, and recruited a total of 75 patients. At the second stage, 28 out of 63 evaluable patients receiving vandetanib achieved PFS at 3 months. The alternative hypothesis that the PFS rate at 3 months is at least 50% was accepted. The median PFS was 2.7 months (95% CI, 1.9-4.4 months) in the vandetanib arm and 1.7 months (95% CI, 0.9-2.6 months) in the placebo arm. The most common adverse events in patients receiving vandetanib were rash (77.3%) and diarrhea (60.0%).


CONCLUSIONS
Maintenance therapy with vandetanib for patients with NSCLC after standard platinum doublet chemotherapy is well tolerated and may prolong PFS compared with placebo, and needs additional investigation.
Department of Medicine, Samsung Medical Center, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
Jin Seok
JS
Ahn
Ki Hyeong
KH
Lee
Jong-Mu
JM
Sun
Keunchil
K
Park
Eun-Suk
ES
Kang
Eun Kyung
EK
Cho
Dae Ho
DH
Lee
Sang-We
SW
Kim
Gyeong-Won
GW
Lee
Jin-Hyoung
JH
Kang
Jong-Seok
JS
Lee
Jae-Won
JW
Lee
Myung-Ju
MJ
Ahn
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D005076:Exanthema / Q000209:etiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D017671:Platinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D010880:Piperidines; D017671:Platinum Compounds; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C452423:vandetanib
Chemotherapy; Lung cancer; Maintenance; Progression-free survival; Target therapy; Vandetanib