846P - Medical optimization of torisel (MOTOR): a phase II trial of temsirolimus as second-line treatment for advanced RCC by the Italian Kidney Cancer Gro...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Renal Cell Cancer
Therapy
Biological therapy
Presenter Michele Milella
Authors M. Milella1, G. Di Lorenzo2, A. Felici1, M. Aieta3, G. Lo Re4, C. Boni5, E. Aitini6, E. Villa7, S. De Placido2, F. Cognetti8
  • 1Divisione Di Oncologia Medica A, Istituto Nazionale Tumori Regina Elena, 00144 - Roma/IT
  • 2Department Of Oncology, Cattedra di Oncologia Medica, Università degli Studi Federico II, 80131 - Napoli/IT
  • 3Medical Oncology, Department of Medical Oncology, National Institute of Cancer, Rionero in Vulture (PZ)., 70122 - Rionero (PZ)/IT
  • 4Oncology, Medical Oncology, Pordenone/IT
  • 5Oncology Dept., Arcispedale S. Maria NuovaDivisione di Oncologia, IT-42100 - Reggio Emilia/IT
  • 6Med. Oncology & Hematology Dept., Ospedale C. Poma, IT-46100 - Mantova/IT
  • 7Medical Oncology, Istituto Scientifico S. Raffaele - IRCCS, Rome/IT
  • 8Division Medical Oncology A, Istituto Nazionale Tumori Regina Elena, 00144 - Roma/IT

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 <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. Final analysis will be presented at the meeting.

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.