222P - Interleukin-8 (IL8) as a biomarker of response and survival with anti-angiogenic agents: a proof-of-concept from the pazopanib (PZP) series in uroth...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Urothelial Cancers
Translational Research
Presenter Andrea Necchi
Authors A. Necchi1, L. Mariani2, N. Zaffaroni3, N. Nicolai4, P. Giannatempo5, C. Morosi6, M.G. Daidone7, A.M. Gianni8, F.G.M. De Braud9, R. Salvioni4
  • 1Medical Oncology/urology Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Biostatistics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3Experimental Oncology And Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 4Surgery Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 5Dept. Genitourinary, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 6Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 7Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 8Medical Oncology, University of Milan - Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 9Division Of Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, IT-20133 - Milano/IT

Abstract

Introduction

Discouraging results have been achieved with salvage therapy for refractory UC. Final results of INT70/09 trial of PZP in 41 multi-relapsed or refractory patients (pts) were promising and the primary endpoint of objective responses was met as 7 pts (17%) had a confirmed PR, 24 had a SD (76% clinical benefit) after independent review (AACR & ASCO 2012). Final achievements on the role of IL8 are presented.

Material and methods

From 02/2010 to 07/2011, 41 pts received PZP 800 mg once daily until PD or unacceptable toxicity. 50 mL of EDTA blood samples were collected at baseline and q4wks together with disease restaging in all pts to analyze plasma levels of VEGF, sVEGFR-1,-2 and -3, c-Kit, HGF, IL-6, 8 and 12 by multiplex ELISA plates. Marker levels were analysed with the Kruskal-Wallis test for pre-post changes, with the covariance analysis and a flexible logistic regression model and with a multivariate Cox regression model to evaluate the relation with response probability and overall survival (OS), respectively.

Results

Significant increase from T0 (baseline) to T1 (+4wks) level was observed for VEGF (p < 0.0001), HGF (p = 0.017), IL6 (p < 0.0129) and IL8 (p < 0.0013) and decrease for VEGFR2 and c-Kit (p < 0.0001 each). Rising IL8(T1) levels significantly associated with RECIST progression at covariance analysis (p = 0.0104). Elevated IL8(T1) levels (IQ range, HR = 2.11), liver mets (HR = 2.33), PS (HR = 3.73) and upper tract UC (HR = 0.33) were significant variables for OS at multivariate Cox analysis. Pts having IL8(T1) levels < 80 pg/ml had significantly greater response (approaching 80%) and 6-month survival (60%) probability than those with a level ≥ 80, for whom a dramatic fall was observed.

Conclusions

The role of IL8 in relation to the development of resistance and shorter survival was demonstrated in the clinic and 2 distinct populations were early recognized. If confirmed on larger series, levels of IL8 ≥80 pg/ml after 4 wks would be used to early decide to switch/interrupt antiangiogenic drugs, with relevant cost-saving advantages. A sequence with an anti-IL8 is characterising our current research.

Disclosure

All authors have declared no conflicts of interest.