PAZOPANIB FOR CERVICAL CANCER?

Pazopanib, an oral agent targeted against vascular endothelial growth factor (VEGF) pathways, is approved for the treatment of advanced renal cell carcinoma. Lapatinib, an oral dual anti-EGFR (epidermal growth factor receptor) and anti-HER2/neu tyrosine kinase inhibitor, is approved for use in certain breast cancer patients.

Dr. Bradley J. Monk from University of California Irvine Medical Center, Orange, California, and colleagues compared outcomes of women with advanced or recurrent cervical cancer treated with pazopanib (74 patients), lapatinib (78 patients), or both (76 patients) in a phase II trial.

The combination arm was discontinued at the interim analysis because it was obviously no better than lapatinib therapy alone and furthermore, combined therapy had a higher rate of fatal serious adverse events and discontinuation for adverse events (17%) compared with lapatinib (5%) and pazopanib (12%).

Median progression-free survival was longer with pazopanib than lapatinib (18.1 vs 17.1 weeks; p < 0.013), although this difference is of questionable clinical significance.

Median overall survival was 11.6 weeks longer with pazopanib (50.7 weeks) than lapatinib (39.1 weeks; p = 0.045) -- although the researchers say "postdiscontinuation antineoplastic therapy may have had an impact on overall survival, and these results need to be interpreted with caution."

Nine percent in the pazopanib group and 5% in the lapatinib group had confirmed tumor responses, whereas unconfirmed response rates were 19% in the pazopanib arm and 9% in the lapatinib arm.

Most adverse events were grade 1 or 2. Fewer patients in the lapatinib group experienced any grade of adverse event (92%), compared with the pazopanib group (96%) and the combination group (95%).

One percent of patients on lapatinib or combination therapy, but no one taking pazopanib, had absolute decreases in left ventricular ejection fraction. Liver enzyme elevations were seen most often in the pazopanib group.

"Antiangiogenesis is a validated target in treating cervical cancer," the researchers conclude. "This trial adds to the existing literature supporting this paradigm and suggests the superiority over ErbB-based approaches such as anti-EGFR and anti-HER2/neu therapy."

"Oral tyrosine kinases such as pazopanib are obviously more convenient than intravenous monoclonal antibodies," the authors add, "but larger phase III trials in cervical cancer are needed to better assess the clinical benefit of both antivascular approaches."

The trial was supported by GlaxoSmithKline, which manufactures both pazopanib and lapatinib. The company employs four of the paper's 10 authors and supports the other six with research funding.

SOURCE: Abstract

J Clin Oncol 2010.