Neoadjuvant temsirolimus in high-risk renal cell carcinoma: Results from a single-center prospective study.

387 Background: The current first-line treatment for advanced renal cell carcinoma (RCC) includes targeted therapy with or without cytoreductive radical nephrectomy. There is a paucity of data as to the effectiveness of adjuvant and neoadjuvant treatment before radical nephrectomy for localized high-risk or advanced disease. We initiated a trial of neoadjuvant Temsirolimus before radical nephrectomy for locally advanced and metastatic RCC examining tumor response and survival. Methods: Patients who presented with advanced RCC were offered enrolment into a prospective, single-centre, ethics approved trial with 12 weeks of temsirolimus before radical nephrectomy. Biopsy tissue was obtained at enrollment and at time of cytoreductive nephrectomy for diagnosis. Patients were administered 25 mg in temsirolimus on a weekly basis for 12 weeks, and then underwent radical nephrectomy. Computed tomography scans and biomarkers were obtained on enrolment, 6 weeks and 12 weeks (before nephrectomy). Ongoing outcome and survival data were analyzed. Results: Eight patients were enrolled into the trial. Patient #1 (10-cm renal mass with bulky adenopathy T2N2M0) had no evidence of disease (NED) at 6 months post-nephrectomy. Patient #2 (9-cm renal mass, bulky adenopathy, pulmonary metastases T2N2M1) also had NED at 6 months postnephrectomy. Patients #3 and #4 experienced regression of the primary mass and have recently undergone uneventful surgery with follow-up pending. Patients #5 and #6 expired prior to the full course of therapy, but had diagnoses other than RCC. Patient #7 experienced disease progression, however, this patient's nephrectomy was delayed by 3 months due to an unrelated myocardial infarct. Patient #8 experienced adverse events. Conclusions: Our findings suggest that neoadjuvant temsirolimus before radical nephrectomy for advanced RCC may improve disease regression post-surgery, and may lead to disease resolution in patients with low-volume disease. Randomized studies with longer term follow-up is necessary to assess overall progression-free survival and overall survival. [Table: see text]