852P - Predictive value of time to best response for efficacy mTOR inhibitors (mTORi) in metastatic renal cell carcinoma (mRCC) patients (pts)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Reza-Thierry Elaidi
Authors R. Elaidi1, C. Teghom2, A. Comte2, M. Jebali2, J. Fouque3, J. Medioni4, S. Oudard5
  • 1Oncology, hospital G.Pompidou, 75015 - paris/FR
  • 2Medical Oncology Service, Hopital European George Pompidou, 75015 - Paris/FR
  • 3Pharmacy, Hopital Europeen Georges-Pompidou, Paris/FR
  • 4Medical Oncology, Georges Pompidou Hospital and Rene Descartes University, 75015 - Paris/FR
  • 5Medical Oncology Service, Georges Pompidou Hospital and Rene Descartes University, 75015 - Paris/FR

Abstract

Background

mTORi usually induce stable disease but some patients present with a rapid objective response. In order to predict early those patients susceptible to respond to mTORi, we investigated the relationship between time to best response and time to progression.

Methods

Data were retrospectively collected in patients treated with mTORi (Ev:everolimus, Tem:temsirolimus) for mRCC in 1st to 4th line setting at the European G. Pompidou Hospital in Paris between 2007 and 2011. Time to best response was obtained from CT-scan and objective response assessed according to RECIST 2.0. Efficacy was assessed by time to progression (TTP) from initiation of 1st mTORi until disease progression/death. Overall survival (OS) was defined as the time from 1st mTOR to death/last contact. Kaplan-Meier estimates with Log-Rank test were used for categorical data. Cox model was used for continuous data and hazard ratios calculation. Only pts having received at least 1 cycle of mTORi were included.

Results

Among the 75 pts, 63 presented with a documented response: PR = 6, SD = 40, PD = 17. 12 pts were excluded for mTORi discontinuation due to toxicity before any response assessment or uncertain date of best response. The 63 eligible pts had a median age = 61 (range: 28-86), sex ratio = 51/12, Ev/Tem = 37/26. Line setting: 1st =7, 2nd =17, 3rd =19, 4th = 17, 5th = 3. Median follow-up time = 22.8m. Time to progression= 7.3m (95%CI: [4.3–9.1]). Time to best response: SD = 2.3 (0.7–8.2), PR = 7.6 (0.7–18.8), PD = 2.1 (0.9–5.0). Time to best response was significantly associated with TTP (N = 46, 35 events, HR = 0.86, 95% CI [0.76–0.97], p = 0.014), but also OS (N = 46, 31 events, HR = 0.83, 95% CI [0.70-0.98], p = 0.03]), an early response leading both to a more rapid progression and being of poor prognosis.

Conclusions

Time to best response was significantly associated to time to progression and overall survival in pts treated with mTORi for mRCC. Given the small sample and the rough assessment of RECIST criteria, further study is needed to investigate the real value of percentage in tumor decrease at each evaluation and velocity of response as a more precise predictive marker of efficacy for these drugs.

Disclosure

S. Oudard: Advisory board to disclose: Sanofi Aventis, Bayer, Novartis, Roche, Pfizer Compensated consultant relatioship to disclose: Novartis, Roche Honoraria to disclose: Sanofi Aventis, Bayer, Novartis, Roche, Pfizer

All other authors have declared no conflicts of interest.