Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer.
OBJECTIVE
Aberrant vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) signaling have been shown to play a role in non-small-cell lung cancer (NSCLC) pathogenesis and are associated with decreased survival. We evaluated the clinical activity and tolerability of sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor that blocks the activity of receptors for VEGF and PDGF, as well as related tyrosine kinases in patients with previously treated, advanced NSCLC.


METHODS
Patients with stage IIIB or IV NSCLC for whom platinum-based chemotherapy had failed received 50 mg/d of sunitinib for 4 weeks followed by 2 weeks of no treatment in 6-week treatment cycles. The primary end point was objective response rate (ORR); secondary end points included progression-free survival, overall survival, and safety.


RESULTS
Of the 63 patients treated with sunitinib, seven patients had confirmed partial responses, yielding an ORR of 11.1% (95% CI, 4.6% to 21.6%). An additional 18 patients (28.6%) experienced stable disease of at least 8 weeks in duration. Median progression-free survival was 12.0 weeks (95% CI, 10.0 to 16.1 weeks), and median overall survival was 23.4 weeks (95% CI, 17.0 to 28.3 weeks). Therapy was generally well tolerated.


CONCLUSIONS
Sunitinib has promising single-agent activity in patients with recurrent NSCLC, with an ORR similar to that of currently approved agents and an acceptable safety profile. Further evaluation in combination with other targeted agents and chemotherapy in patients with NSCLC is warranted.
Socinski
Mark A
MA
Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, CB# 7305, Chapel Hill, NC 27599, USA. socinski@med.unc.edu
Novello
Silvia
S
Brahmer
Julie R
JR
Rosell
Rafael
R
Sanchez
Jose M
JM
Belani
Chandra P
CP
Govindan
Ramaswamy
R
Atkins
James N
JN
Gillenwater
Heidi H
HH
Pallares
Cinta
C
Tye
Lesley
L
Selaru
Paulina
P
Chao
Richard C
RC
Scagliotti
Giorgio V
GV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002423:Cause of Death; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D010146:Pain / Q000139:chemically induced; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D013280:Stomatitis / Q000139:chemically induced; D000077210:Sunitinib; D016896:Treatment Outcome
D007211:Indoles; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D002945:Cisplatin; D000077210:Sunitinib