Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study.
OBJECTIVE
This phase II study evaluated efficacy and safety of single-agent axitinib, an oral, potent, selective inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, in patients with advanced non-small-cell lung cancer (NSCLC).


METHODS
This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received a starting dose of axitinib 5 mg orally BID. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response rate. Secondary end points included safety and tolerability, overall survival (OS), and progression-free survival (PFS).


RESULTS
Thirty-two patients were enrolled, with a median age of 66.5 years. The majority of patients (75%) had adenocarcinoma. Nine patients (28%) had received no prior chemotherapy for metastatic disease, and 23 (72%) had received > or = one regimen. Three patients (9%) had a RECIST investigator-assessed, confirmed partial response (PR); disease control rate (PR + stable disease) was 41%. Median PFS was 4.9 months overall (95% CI, 3.6 to 7.0 months). Median OS was 14.8 months (95% CI, 10.7 months to not estimable) overall and 14.8 months (95% CI, 12.5 months to not estimable) in patients receiving first-line axitinib. One-year survival rates for patients with or without prior therapy for metastatic disease were 57% and 78%, respectively. Grade 3 treatment-related adverse events in > or = 5% of patients comprised fatigue (22%), hypertension (9%), and hyponatremia (9%).


CONCLUSIONS
Axitinib demonstrated single-agent activity in patients with advanced NSCLC. Therapy was well tolerated with manageable toxicities. Further investigation of this VEGFR inhibitor in NSCLC is of interest.
Schiller
Joan H
JH
University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8852, USA. joan.schiller@utsouthwestern.edu
Larson
Timothy
T
Ou
S-H Ignatius
SH
Limentani
Steven
S
Sandler
Alan
A
Vokes
Everett
E
Kim
Sinil
S
Liau
Katherine
K
Bycott
Paul
P
Olszanski
Anthony J
AJ
von Pawel
Joachim
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077784:Axitinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; D040262:Receptors, Vascular Endothelial Growth Factor