Stopping Renal Cell Carcinoma (mRCC) Drugs Induces Tumor Flare
Tumor flare from discontinuation of sunitinib and pazopanib associated with decreased survival.
Discontinuing sunitinib and pazopanib treatment results in acceleration of tumor growth rate and induces tumor flare in patients with metastatic renal cell carcinoma (mRCC), which can lead to worse survival, according to a new study.
Roberto Iacovelli, MD, of Gustave Roussy in Villejuif, France, and colleagues studied 63 patients with mRCC treated with first-line sunitinib or pazopanib—both tyrosine kinase inhibitors—at standard dosages. All had discontinued treatment because of disease progression, intolerable toxicity, or sustained response (partial response/stable disease).
Subjects had their tumor growth rates evaluated immediately before treatment (GR1) and after immediately treatment discontinuation (GR2). The investigators calculated tumor flare by substracting GR1 from GR2). The main study outcome was overall survival.
The median duration of treatment was 9.3 months. The median progression-free survival was 11.1 months, and the median overall survival was 41.5 months. The reasons for treatment discontinuation were disease progression (61.9% of cases), toxicity (22.2%), and sustained response (15.9%).
The median GR1 was 0.16 cm per month and the median GR2 was 0.70 cm per month, Dr. Iacovelli's group reported online ahead of print in European Urology. In the overall population, the median tumor flare was 0.55 cm per month, and differed according to the reason for discontinuation.
It was 1.66 cm per month for disease progression, 0.95 cm per month for toxicity, and 0.15 cm per month for sustained response. In adjusted analyses, tumor flare was associated with an 11% increased risk for death from the time of treatment discontinuation.
Patients with GR1 less than the median had significantly greater overall survival than patients with GR1 greater than or equal to the median (51.6 vs. 12.3 months). Patients with GR2 less than the median had significantly greater overall survival than those with GR2 greater than or equal to the median (51.6 vs. 15.1 months).
The study provides the first clinical evidence that discontinuing sunitinib or pazopanib results in acceleration of tumor growth rate, and thereby negatively affects the prognosis of mRCC patients, the researchers stated.