Using presurgical sunitinib to select patients with newly diagnosed metastatic clear cell renal cell carcinoma for cytoreductive nephrectomy: A phase II study.

Abstract

371^ Background: Timing of cytoreductive nephrectomy (CN) is still a matter of debate in mRCC. This study was designed to test the hypothesis that lead-in treatment with sunitinib (Su) selects patients (pts) most likely to benefit from nephrectomy, and can aid in assessing determinants of response and resistance. Methods: Pts with biopsy proven, newly diagnosed clear cell mRCC with measurable disease, performance status of 0/1, and resectable primary tumor were eligible. Pts received one cycle of sunitinib 50mg PO QD on a 28 day on/14 day off cycle, were restaged, and if stable/responding underwent nephrectomy between day 7 and 21 of second cycle of Su. If disease remained stable on postop scans, pts continued Su. Mutations in a 200 gene cancer gene panel as well as copy number variation were used to correlate molecular changes with clinical outcome. Results: 50 pts were enrolled: 36 (72%) were male and 38 (76%) Caucasian, Median age 61 years (range: 43–84). 44 had intermediate MSKCC score and 6 were poor risk. 45 pts (90%) were evaluable. No drug-related perioperative complications were noted. A total of 9 (18%) pts did not have nephrectomy: 6 because of progression, 2 because of drug related toxicity, and one who required emergency surgery during the first cycle for bowel obstruction. Median primary tumor shrinkage after 1 cycle was 4 percent (range -18 to +11%). 4 (8%) pts were found to have nonclear cell pathology at nephrectomy (2 sarcomatoid, 1 papillary, 1 unclassified). Among the 45 evaluable pts, the median PFS was 8.7 months (95% CI: 5.8 – 37.3 months). 24 (53%) pts came off for progressive disease, and five (11%) pts came off for toxicity. With a median follow-up time of 27.3 months, median OS was 32.2 months (95% CI: 17.2 – Not estimable). To date, 20 (40%) pts have died. Copy number and genomic data analysis are underway, and will be presented and correlated with clinical outcome. Conclusions: Pretreatment with Su safely triaged mRCC pts into nephrectomy versus nonnephrectomy groups, with acceptable efficacy and OS. Ongoing studies will define molecular characteristics defining subgroups most likely to benefit from Su. Clinical trial information: NCT00715442.