863P - Predictive factors of survival for patients with bladder cancer (BC) in phase I clinical trials

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Urothelial Cancers
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Vasiliki Michalarea
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors V. Michalarea1, S. Rafii1, R. Kumar1, K. Rihawi1, H.N. Toloui1, R. Huddart2, S.B. Kaye1, U. Banerji3, J.S. De Bono4, L.R. Molife3
  • 1Drug Development Unit, The Istitute of Cancer Research and the Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 2Clinical Oncology, Royal Marsden Hospital Institute of Cancer Research, SM2 5PT - Sutton/GB
  • 3Cr-uk Cancer Therapeutics Unit, Drug Development Unit, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5NG - Sutton/GB
  • 4Drug Development Unit, The Institute of Cancer Research & The Royal Marsden NHS Trust, SM2 5PT - Sutton/GB




There are limited anticancer therapies available for BC. Novel targeted therapies (TT) may offer more treatment options.


Retrospective data was collected on clinical treatment and tumour characteristics on patients (pts) with BC treated in the Drug Development Unit, at the Royal Marsden Hospital (RMH) between August 1996 and January 2014.Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model, and associations were tested with Fischer's Exact test.


125 pts with BC were referred and 36 (29%) were treated. Median age was 58 yrs (range: 30-68). 7 female, 38% ECOG 0 and 62% ECOG 1-2. Histological types included: transitional cell (n = 24), squamous cell (n = 2), urachal (n = 2), papillary cell (n = 2) and adenocarcinoma (n = 2). 51% pts had 1 line of prior treatment, 33% 2 lines and 16% ≥3 lines.Pts were treated on 20 phase 1 trials; 6 trials were combination chemotherapy and TT, and 14 trials were single agents, targeting: PI3K (n = 3), HDAC (n = 3), EGFR/VEGFR (n = 3), oncolytic viruses (n = 2), mTOR (n = 1), AKT (n = 1), PARP (n = 1), TS (n = 1), c-MET (n = 1), nucleoside (n = 1), microtubule (n = 1), Rho (n = 1) and Bcl2 (n = 1). Median time on trial was 1.8 months (m; range: 0.1 -15.6).Objective response rate was 14%, and the clinical benefit rate (CBR: CR + PR + SD) was 47%, as defined by RECIST 1.0. Median overall survival (OS) for pts with a CB was 9.2 m versus 3.3 m for pts with progressive disease (HR0.29, CI 0.07-0.037,P < 0.0001). In univariate analysis, superior OS was favoured by RMH score 0-1 (HR0.33, CI 0.05-0.55,P = 0.004), and white cell count (WCC) <10.5x109/L(HR 0.40,CI 0.08-0.80,P = 0.047). Lines of prior treatment, platelet count and ECOG were not predictive of OS. In a multivariate model, CB and WCC <10.5x109/L remained predictive of OS, however RMH score did not. There was no interaction between RMH score and WCC.


Predictors of OS for BC patients on phase I clinical trials include CB and WCC. The number of BC pts treated is low, although outcomes are comparable to the general phase I patient population. With the limited treatment options available for this group, phase 1 trial participation should be considered at an earlier stage for these patients.


All authors have declared no conflicts of interest.