Abstract LB-226: mTOR inhibition by Temsirolimus as second-line treatment for advanced RCC: The Medical optimization of Torisel® (MoTOR) phase II trial by the Italian Kidney Cancer Group (GIR)
Authors: Milella Michele , Felici Alessandra , Lorenzo Giuseppe Di , Aieta Michele , Ardito Raffaele , Boni Corrado , Rondini Ermanno , Aitini Enrico , Villa Eugenio , Re Giovanni Lo , Algeri Renato , Foa Paolo , Amoroso Domenico , Moscetti Luca , Gallucci Michele , Giannarelli Diana , Placido Sabino De , Cognetti Francesco ,   on behalf of the GIR2 investigators.
Published: August 2012

Background: The mammalian target of rapamycin (mTOR) kinase is an essential regulator of growth and response to hypoxic and metabolic stress and a well-established therapeutic target in renal cell carcinoma (RCC). The mTOR inhibitor Temsirolimus (CCI-779, Torisel®) is the first-line treatment of choice for RCC patients with poor-risk features. Preclinical and clinical evidence indicates that mTOR inhibitors may be effective in controlling RCC growth, even after resistance to agents targeting the VEGF/VEGFR axis ensues. Thus we designed a multicenter phase II trial to assess the activity and safety of Temsirolimus as II-line treatment for advanced RCC patients (pts). Methodology: This was an open-label, multicenter, phase II trial of Temsirolimus (25 mg/wk i.v.), administered to advanced RCC pts with documented progression after 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%. Pts who underwent any other I-line treatment were allowed on study until the target accrual in the sunitinib-pretreated group was met. 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. 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 &lt;10% of weekly administrations omitted and 15/67 (22%) pts requiring dose reductions (to 20 mg/wk and 15 mg/wk in 11 and 4 pts, respectively). Mean number of weekly administrations received was 15. Conclusions. Temsirolimus is an active and well-tolerated II-line treatment for advanced RCC, particularly in sunitinib-pretreated pts, and may constitute a suitable therapeutic option in this setting.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-226. doi:1538-7445.AM2012-LB-226