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

作者：Scagliotti Giorgio V^*; Felip Enriqueta; Besse Benjamin; von Pawel Joachim; Mellemgaard Anders; Reck Martin; Bosquee Lionel; Chouaid Christos; Lianes Barragan Pilar; Paul Elaine M; Ruiz Soto Rodrigo; Sigal Entisar; Ottesen Lone H; LeChevalier Thierry

来源：Journal of Thoracic Oncology, 2013, 8(12): 1529-1537.

DOI：10.1097/JTO.0000000000000005

• Non-small-cell lung cancer
• Pazopanib
• Pemetrexed
• Cisplatin

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. %26lt;br%26gt;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). %26lt;br%26gt;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). %26lt;br%26gt;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.

• 出版日期2013-12