846P - Medical Optimization of Torisel® (MOTOR): A Phase II Trial of Temsirolimus as Second-Line Treatment for Advanced RCC by the Italian Kidney Cancer Group (GIR)

Abstract

ABSTRACT Purpose The mammalian target of rapamycin (mTOR) kinase is a well-established therapeutic target in renal cell carcinoma (RCC). We explored the activity and safety of Temsirolimus as II-line treatment for advanced RCC pts in a multicenter phase II trial. Methodology in this open-label trial, Temsirolimus (25 mg/wk i.v.) was administered to advanced RCC pts with documented progression after any I-line treatment. Primary endpoint was PFS rate at 6 mos. Tumor response was assessed every 8 wks. Considering a 6-mo PFS rate of 20% unacceptable (p0 = 20%) and a 6-mo PFS rate of 40% (p1 = 40%) of interest, a minimum targeted accrual of 47 pts in the sunitinib-pretreated group was to be pursued in order to reach 90% power at a significance level of 5%. Results From May 2009 to January 2012, 76 pts were enrolled (median age: 67 yrs, range: 36-86; M/F: 58/18; ECOG PS 0/1/2: 51/19/6); I-line therapy included sunitinib (60 pts), bevacizumab (8), sorafenib (3), cytokines (2), or other (3). With 18/57 evaluable patients free from progression at 6 mos in the sunitinib-pretreated group the primary endpoint was met and trial accrual was stopped. Median PFS was 4.0 mos (95% CI: 2.7–5.3) and 4.6 mos (95% CI: 2.8–6.5) in the overall (n = 71) and sunitinib-pretreated (n = 57) populations, respectively; OS in the same groups was 13.7 mos (95% CI: 9.1–18.3) and 14.6 mos (95% CI: 8.9-20.3), respectively. Six out of 71 pts (8%) had PR and 33/71 (46%) had SD as their best response. Toxicity (n = 68) was mild with G3 anemia, neutropenia and thrombocytopenia in 2, 1, and 1 pts, respectively; G3 hyperglycemia and G3 hypertriglyceridemia in 2 and 7 pts, respectively; G4 hypercholesterolemia in 2 pts; G3 stomatitis in 5 pts; G3 asthenia in 3 pts; G3-4 pulmonary toxicity in 2 pts; G3 diarrhea in 2 pts; G3 cutaneous rash in 1 pt. Only 1 hypersensitivity reaction occurred during Temsirolimus infusion. Treatment compliance was good, with Conclusions Temsirolimus is an active and well-tolerated II-line treatment for advanced RCC; results of currently ongoing phase III trials are awaited to further define its role in this setting. Disclosure All authors have declared no conflicts of interest.