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

BMC Cancer

Giorgio V Scagliotti³  Sinil Kim⁴  Antonella Ingrosso⁵  Andreas G Niethammer⁴  Paul Bycott⁴  Jie Tang⁷  Silvia Novello³  Artem Poltoratskiy⁶  Igor M Bondarenko¹  Nobuyuki Yamamoto²  Chandra P Belani⁸ 

[1]Department of Oncology and Medical Radiology, Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine

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

[3]Department of Oncology, San Luigi Hospital, University of Torino, Torino, Italy

[4]Clinical Development, Pfizer Oncology, San Diego, CA, USA

[5]Clinical Development, Pfizer Oncology, Milano, Italy

[6]Department of Thoracic Oncology, St. Petersburg Medical University, St. Petersburg, Russia

[7]Oncology Business Unit, Pfizer Inc, New York, NY, USA

[8]Penn State Milton S. Hershey Medical Center, Penn State Hershey Cancer Institute, Hershey, PA, USA

关键词: NSCLC;    Non-squamous;    Cisplatin;    Pemetrexed;    Axitinib;   

Others  :  858867
DOI  :  10.1186/1471-2407-14-290

 received in 2013-12-17, accepted in 2014-04-17,  发布年份 2014

【 摘 要 】

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).

【 授权许可】

   
2014 Belani et al.; licensee BioMed Central Ltd.

【 图 表 】

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