Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer.

Abstract

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%).

CONCLUSION:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00768755 (October 7, 2008).

• Authors: Chandra P Belani, Nobuyuki Yamamoto, Igor M Bondarenko, Artem Poltoratskiy, Silvia Novello, Jie Tang, Paul Bycott, Andreas G Niethammer, Antonella Ingrosso, Sinil Kim, Giorgio V Scagliotti
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 290 (Apr 25 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 24766732 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Imidazoles
• Indazoles
• Vascular Endothelial Growth Factor A
• Pemetrexed
• Guanine
• Axitinib
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols
• Axitinib
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cisplatin (administration & dosage)
• Disease-Free Survival
• Female
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Imidazoles (administration & dosage)
• Indazoles (administration & dosage)
• Male
• Middle Aged
• Pemetrexed
• Vascular Endothelial Growth Factor A (genetics)