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Open Access Research article

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

Chandra P Belani1*, Nobuyuki Yamamoto2, Igor M Bondarenko3, Artem Poltoratskiy4, Silvia Novello5, Jie Tang6, Paul Bycott7, Andreas G Niethammer7, Antonella Ingrosso8, Sinil Kim7 and Giorgio V Scagliotti5

Author Affiliations

1 Penn State Milton S. Hershey Medical Center, Penn State Hershey Cancer Institute, Hershey, PA, USA

2 Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

3 Department of Oncology and Medical Radiology, Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine

4 Department of Thoracic Oncology, St. Petersburg Medical University, St. Petersburg, Russia

5 Department of Oncology, San Luigi Hospital, University of Torino, Torino, Italy

6 Oncology Business Unit, Pfizer Inc, New York, NY, USA

7 Clinical Development, Pfizer Oncology, San Diego, CA, USA

8 Clinical Development, Pfizer Oncology, Milano, Italy

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BMC Cancer 2014, 14:290  doi:10.1186/1471-2407-14-290

Published: 25 April 2014

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/m2 and cisplatin 75 mg/m2 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).

Keywords:
Axitinib; Pemetrexed; Cisplatin; Non-squamous; NSCLC