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Predictive Factors of Survival for Patients with Bladder Cancer (Bc) in Phase I Clinical Trials
Annals of Oncology 25 (Supplement 4): iv280–iv304, 2014 doi:10.1093/annonc/mdu337.56
genitourinary tumours, non-prostate 863P
PREDICTIVE FACTORS OF SURVIVAL FOR PATIENTS WITH BLADDER CANCER (BC) IN PHASE I CLINICAL TRIALS
abstracts
Background: There are limited anticancer therapies available for BC. Novel targeted therapies (TT) may offer more treatment options. Methods: 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
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv300/2241583 by guest on 26 October 2019
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 1 Drug Development Unit, The Istitute of Cancer Research and the Royal Marsden NHS Foundation Trust, Sutton, UK 2 Clinical Oncology, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK 3 CR-UK Cancer Therapeutics Unit, Drug Development Unit, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, Sutton, UK 4 Drug Development Unit, The Institute of Cancer Research & The Royal Marsden NHS Trust, Sutton, UK
hazards model, and associations were tested with Fischer’s Exact test. Results: 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. Conclusions: 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. Disclosure: All authors have declared no conflicts of interest.
genitourinary tumours, non-prostate 863P
PREDICTIVE FACTORS OF SURVIVAL FOR PATIENTS WITH BLADDER CANCER (BC) IN PHASE I CLINICAL TRIALS
abstracts
Background: There are limited anticancer therapies available for BC. Novel targeted therapies (TT) may offer more treatment options. Methods: 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
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv300/2241583 by guest on 26 October 2019
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 1 Drug Development Unit, The Istitute of Cancer Research and the Royal Marsden NHS Foundation Trust, Sutton, UK 2 Clinical Oncology, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK 3 CR-UK Cancer Therapeutics Unit, Drug Development Unit, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, Sutton, UK 4 Drug Development Unit, The Institute of Cancer Research & The Royal Marsden NHS Trust, Sutton, UK
hazards model, and associations were tested with Fischer’s Exact test. Results: 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. Conclusions: 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. Disclosure: All authors have declared no conflicts of interest.