Randomized prospective phase II trial of two schedules of sorafenib daily and interferon-α2a (IFN) in metastatic renal cell carcinoma (RAPSODY): GOIRC Study 0681

Abstract

5100 Background: Sorafenib is an oral multi-kinase inhibitor with a demonstrated efficacy in MRCC (Eisen, ASCO 2006). IFN is a pleiotropic molecule with an antiangiogenic activity probably dose and schedule-dependent (Folkman, 1992). Aim of this study was to evaluate the activity and safety of sorafenib combined with IFN in two different schedules. Methods: Eligible patients had metastatic renal cell carcinoma (MRCC) with a clear cell component = 50%, previous nephrectomy, ECOG Performance Status 0–2, no cerebral metastases or previous treatment, measurable disease; any Motzer’s score was allowed. Patients received oral sorafenib 400mg BID continuously plus sc IFN, 9 MU three times a week (arm-A) or 3 MU five times a week (arm-B), started 7 days after sorafenib to increase compliance. Planned sample size of this single-stage study was 100 cases to be enrolled over 18 months. Primary end points: Progression Free Survival (PFS) in the two arms and safety; secondary end-points: overall response (intention-to treat analysis) and overall survival. Results: Between January 2006 and January 2007 all the expected cases were enrolled into the study (median age 63 years, range 34–82; male/female: 71/29). Of 63 patients for whom a post baseline assessment was available (31 in arm A and 32 in arm B), 16 achieved a partial response (25.4%: 29% in arm A, 95% CI 13.2–44.9 and 22% in arm B, 95% CI 7.6–36.2), 26 had a stable disease (41.3%: 29% in arm A and 53% in arm B) and 21 progressed (33.3%: 42% in arm A and 25% in arm B). Due to the short follow-up period PFS data are not yet available. The most common grade 3/4 toxicities affecting more than 5% of the pts were equally distributed between arms except for fatigue and skin rash (respectively 19% and 8%, only arm A): hypophosphatemia (43%), hand-foot syndrome (22%), anorexia, stomatitis, hyperamylasemia (11% each), diarrhea (8%) and hyperlipasemia (5%). Conclusions: With an overall response rate of 25.4% and a tumor control rate (partial response + stable disease) of 66.7% (58.1% in arm A, 95% CI 40.7–75.5 and 75.0% in arm B, 95% CI 60.0–90.0; p = ns) sorafenib plus IFN can be considered a promising regimen in MRCC. Further investigations of the active and safe low-dose IFN combination arm are warranted. [Table: see text]