NEW YORK (Reuters Health) – Some patients with metastatic clear-cell renal cancer appear to fare relatively well when treated with sunitinib before undergoing planned nephrectomy — even though progression rates are high when sunitinib is suspended during the surgical period, according to a new study reported in European Urology online May 17.
However, the authors caution, “Progression on sunitinib prior to planned nephrectomy has a poor outcome and alternative treatments should be considered.”
Dr. Axel Bex, with the Netherlands Cancer Institute in Amsterdam, and colleagues note that the tyrosine kinase inhibitor sunitinib is established as first-line therapy for clear-cell renal cell carcinoma, but combining it with cytoreductive nephrectomy surgery is controversial.
“A potential treatment option is to give a period of targeted therapy prior to cytoreductive nephrectomy,” the team explains. This strategy may reduce tumor size prior to surgery, and it would identify patients with rapidly progressive disease, thus sparing them from surgery and perhaps switching the focus to other systemic therapies. “However, there are concerns that the treatment break during surgery, which is approximately 1 month, causes tumour rebound and may have a detrimental effect.”
The researchers therefore looked at outcomes of two phase II trials testing upfront sunitinib for 12-16 weeks before nephrectomy in a total of 66 patients with clear-cell tumors.
Sunitinib was discontinued for a median of 29 days during the perioperative period. During the treatment break, 17 patients progressed, but 13 of them stabilized once sunitinib was started again. Nonetheless, “This progression is of concern as it may facilitate the development of sunitinib resistance,” the investigators comment.
Overall survival for the group as a whole was 15.2 months. Stratified by risk, it was only 9.0 months for patients classified as having poor-risk disease, but significantly longer in those with intermediate-risk disease (26.0 months; p<0.01).
The team finds this “encouraging” since overall survival in intermediate-risk patients in the pivotal phase III trial of sunitinib (in which most patients had undergone prior nephrectomy) was 20.7 months.
In the current study, progression of disease before nephrectomy was another independent risk factor for poor prognosis seen on multivariate analysis (hazard ratio 5.34). In this subgroup, “alternative treatments should be considered,” the authors advise.
Dr. Bex and colleagues conclude, “Despite the high progression rate during the surgery-related treatment break, the overall survival with this approach is in line with those seen in the pivotal trials.” Still, they point out that “in the absence of randomised studies it is not possible to determine if this approach is beneficial.”
Reference:
The Outcome of Patients Treated with Sunitinib Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer
Eur Urol 2011.
