Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer.
BACKGROUND
The efficacy and safety of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non-small-cell lung cancer (NSCLC).


METHODS
Overall, 170 patients were randomly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 of up to six 21-day cycles (arm I); axitinib on days 2 through 19 of each cycle plus pemetrexed/cisplatin (arm II); or pemetrexed/cisplatin alone (arm III). The primary endpoint was progression-free survival (PFS).


RESULTS
Median PFS was 8.0, 7.9, and 7.1 months in arms I, II, and III, respectively (hazard ratio: arms I vs. III, 0.89 [P = 0.36] and arms II vs. III, 1.02 [P = 0.54]). Median overall survival was 17.0 months (arm I), 14.7 months (arm II), and 15.9 months (arm III). Objective response rates (ORRs) for axitinib-containing arms were 45.5% (arm I) and 39.7% (arm II) compared with 26.3% for pemetrexed/cisplatin alone (arm III). Gastrointestinal disorders and fatigue were frequently reported across all treatment arms. The most common all-causality grade ≥3 adverse events were hypertension in axitinib-containing arms (20% and 17%, arms I and II, respectively) and fatigue with pemetrexed/cisplatin alone (16%).


CONCLUSIONS
Axitinib in combination with pemetrexed/cisplatin was generally well tolerated. Axitinib combinations resulted in non-significant differences in PFS and numerically higher ORR compared with chemotherapy alone in advanced NSCLC.


BACKGROUND
ClinicalTrials.gov: NCT00768755 (October 7, 2008).
Penn State Milton S, Hershey Medical Center, Penn State Hershey Cancer Institute, Hershey, PA, USA. cbelani@hmc.psu.edu.
Chandra P
CP
Belani
Nobuyuki
N
Yamamoto
Igor M
IM
Bondarenko
Artem
A
Poltoratskiy
Silvia
S
Novello
Jie
J
Tang
Paul
P
Bycott
Andreas G
AG
Niethammer
Antonella
A
Ingrosso
Sinil
S
Kim
Giorgio V
GV
Scagliotti
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D000077784:Axitinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007191:Indazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D005971:Glutamates; D007093:Imidazoles; D007191:Indazoles; D042461:Vascular Endothelial Growth Factor A; D000068437:Pemetrexed; D006147:Guanine; D000077784:Axitinib; D002945:Cisplatin