Novel angiogenesis agent performs well in renal cell carcinoma trials

Stockholm, Sweden-In patients with metastatic renal cell carcinoma treated with the novel compound pazopanib, tumor response could be correlated with several prognostic factors, investigators reported at the European Society for Medical Oncology 33rd Congress here.

Investigators previously reported durable activity with pazopanib, 800 mg given once daily, in a phase II study of 225 patients. After 12 weeks of treatment, responders were allowed to continue receiving the agent until disease progression, while patients with stable disease were randomized to pazopanib or placebo. Independent review of the final efficacy analysis showed that the response rate was 34.7%, median duration of response was 68 weeks, and progression-free survival (PFS) was 11.9 months.

An exploratory analysis was performed to identify potential indicators of pazopanib's efficacy by evaluating baseline patient characteristics, von Hippel-Lindau (VHL) gene status, gene signature, and circulating biomarkers. These results were reported by Thomas E. Hutson, DO, PharmD, director of the genitourinary program at Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas.

The analysis found that Eastern Cooperative Oncology Group (ECOG) performance status of 0 and normal hemoglobin at baseline correlated with tumor response, as did a decrease in soluble VEGFR2, which was highly predictive. Soluble VEGFR2 was also correlated with PFS. In patients with a decrease of 31% or more in this marker, median PFS was 12 months, compared with 10.9 months in patients who had more than a 31% decrease in soluble VEGFR2.

Results of subgroup analysis (including patients randomized to placebo) identified the following factors that correlate with prolonged PFS: ECOG performance score of 0 (median PFS, 59.1 weeks) versus ECOG score of 1 (median PFS, 27.7 weeks, p=.002), and more than one year from diagnosis to treatment (median PFS, 55.9 weeks) versus 1 year or less (median PFS, 28 weeks, p=.001). No other baseline factors were found to affect PFS.

Baseline levels of VEGF and soluble VEGFR1 did not correlate with tumor response or with PFS. Other biological factors also not correlated with tumor response included lactate dehydrogenase levels, serum calcium levels, VHL status, or gene signature. Other unrelated factors included prior nephrectomy, prior systemic therapy, time to recurrence, sites of metastasis, Memorial Sloan-Kettering Cancer Center criteria, age, race, or sex.

"Pazopanib has demonstrated durable anti-tumor activity in advanced RCC, and this is having a positive, clinically significant impact on patient care," Dr. Hutson said.

The treatment was well tolerated. The most common grade 3 or 4 treatment-related adverse events were hypertension (8%), alanine aminotransferase elevations (5%), diarrhea (4%), and fatigue (4%).

Dr. Hutson has received research support from GlaxoSmithKline, Wyeth, Pfizer, Bayer, Keryx, and Genentech.