Clinical Epidemiology and Ageing

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.

Scagliotti GV, Felip E, Besse B, von Pawel J, Mellemgaard A, Reck M, Bosquee L, Chouaid C, Lianes-Barragán P, Paul EM, Ruiz-Soto R, Sigal E, Ottesen LH, Lechevalier T J Thorac Oncol. 2013;8(12):1529-37.

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.

MeSH terms: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Follow-Up Studies; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pemetrexed; Prognosis; Pyrimidines; Sulfonamides; Survival Rate
DOI: 10.1097/JTO.0000000000000005

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