An open-label, multicenter, randomized, phase II study of pazopanib in combination with pemetrexed in first-line treatment of patients with advanced-stage non-small-cell lung cancer.

Abstract

INTRODUCTION:

This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.

METHODS:

Patients were randomized (2:1 ratio) to receive pemetrexed 500 mg/m(2) intravenously once every 3 weeks plus either oral pazopanib 800 mg daily or cisplatin 75 mg/m(2) intravenously once every 3 weeks up to six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. The primary endpoint was progression-free survival (PFS).

RESULTS:

The study was terminated after 106 of 150 patients were randomized due to a higher incidence of adverse events leading to withdrawal from the study and severe and fatal adverse events in the pazopanib/pemetrexed arm than in the cisplatin/pemetrexed arm. At the time enrolment was discontinued, there were three fatal adverse events in the pazopanib/pemetrexed arm, including ileus, tumor embolism, and bronchopneumonia/sepsis. Treatment with pazopanib/pemetrexed was discontinued resulting in more PFS data censored for patients in the pazopanib/pemetrexed arm than those in the cisplatin/pemetrexed arm. There was no statistically significant difference between the pazopanib/pemetrexed and cisplatin/pemetrexed arms for PFS (median PFS, 25.0 versus 22.9 weeks, respectively; hazard ratio = 0.75; 95% confidence interval, 0.43%-1.28%; p = 0.26) or objective response rate (23% versus 34%, respectively; 95% confidence interval, -30.6% to 7.2%; p = 0.21).

CONCLUSION:

The combination of pazopanib/pemetrexed in first-line treatment of non-small-cell lung cancer showed some antitumor activity but had unacceptable levels of toxicity.

• Authors: Giorgio V Scagliotti, Enriqueta Felip, Benjamin Besse, Joachim von Pawel, Anders Mellemgaard, Martin Reck, Lionel Bosquee, Christos Chouaid, Pilar Lianes-Barragán, Elaine M Paul, Rodrigo Ruiz-Soto, Entisar Sigal, Lone H Ottesen, Thierry Lechevalier
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 8 Issue 12 Pg. 1529-37 (Dec 2013) ISSN: 1556-1380 [Electronic] United States
• PMID: 24389434 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Indazoles
• Pyrimidines
• Sulfonamides
• Pemetrexed
• Guanine
• pazopanib
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, mortality, pathology)
• Adenocarcinoma, Bronchiolo-Alveolar (drug therapy, mortality, pathology)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Large Cell (drug therapy, mortality, pathology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Cisplatin (administration & dosage)
• Female
• Follow-Up Studies
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Indazoles
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Pemetrexed
• Prognosis
• Pyrimidines (administration & dosage)
• Sulfonamides (administration & dosage)
• Survival Rate