Abstract 2016P
Background
Recommended treatment for MIBC is radical cystectomy (RC) with cisplatin-based NAD chemotherapy in eligible patients. EFS, a common intermediate endpoint in NAD/perioperative oncology trials, allows for accelerated treatment evaluation while awaiting overall OS results. This study evaluated EFS as a clinical surrogate endpoint for OS in NAD treated MIBC.
Methods
A literature review was conducted to identify clinical trials for NAD therapy prior to RC in MIBC (stage T2-T4a, N0-N1, M0). The trial-level surrogacy was evaluated by assessing the association of hazard ratio (HR) of EFS with the HR of OS; outcome-level surrogacy was evaluated by assessing the associations of survival rates and median survival time between EFS and OS, respectively. These associations were meta-analyzed using linear regression weighted by study sample size. The strength of the association was measured by coefficient of determination (R2). Surrogate threshold effect (STE) was reported indicating the minimum HR of EFS needed to predict a significant HR of OS <1.
Results
A total of 15 eligible clinical trials were identified. The analysis of trial-level surrogacy included 6 RCTs with a total of 1,948 patients; the analyses of outcome-level surrogacy included 21 study arms from 15 trials with 2,509 patients. The log (HR) of EFS was significantly associated with the log (HR) of OS with R2 of 0.94. (Table) The STE was 0.88 for the HR of EFS. Consistently, significant outcome-level associations were observed between 3-year EFS and 5-year OS, median EFS time and median OS time, as well as 1-year EFS and 3-year OS, with R2 ranging from 0.70 to 0.97. (Table) Table: 2016P
Trial-level and outcome-level associations between EFS and OS based on clinical trials for neoadjuvant therapy in MIBC
| Outcomes for comparison | N of observations | Coefficient (P-value) | R 2 (95% CI) | |
| Trial-level surrogacy | HR of EFS vs. HR of OS | 6 RCTs | 1.26 (0.001) | 0.94 (0.74, 1.00) |
| Outcome-level surrogacy | 3-year EFS vs. 5-year OS | 12 study arms | 0.85 (ConclusionsThere is a strong association between EFS and OS in terms of treatment effects and outcome measures in clinical trials for MIBC following NAD therapy. EFS can be considered as a surrogate endpoint for OS for treatment evaluation in the NAD setting for MIBC. Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. FundingMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. DisclosureC.N. Sternberg: Financial Interests, Personal, Other, Honoraria: Merck & Co., Inc., Astellas Pharma, Inc., AstraZeneca, Bayer, Bristol Myers Squibb/Medarex, Foundation Medicine Inc, Sanofi, Genzyme, Gilead Sciences, Inc., Pfizer, Janssen, Roche, Medscape, UroToday. P.J. Squires, H. Li: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. Y. Song, A. Wu, Y. Gao, C. Xu: Financial Interests, Institutional, Other, Employee of Analysis Group, Inc., which has received consultation fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for conducting this work: Merck Sharp & Dohme LLC. R. Kataria: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC. Resources from the same session1997P - Novel biomarker, ephrinB2 (B2), predicts resistance to treatment and poor overall survival (OS) metastatic urothelial carcinoma (mUC)Presenter: Sarmad Sadeghi Session: Poster session 13 1998P - Preliminary results from a phase I study of T3011, an oncolytic HSV expressing IL-12 and anti-PD-1 antibody, for BCG-failure non-muscle-invasive bladder cancer (NMIBC)Presenter: Dingwei Ye Session: Poster session 13 1999P - Expression heterogeneity of ADC-related targets between primary tumors and metastatic lymph nodes in advanced urothelial cancersPresenter: Xingliang Tan Session: Poster session 13 2001P - Epidemiology and treatment patterns of patients with locally advanced or metastatic urothelial cancer in France: A non-interventional database studyPresenter: Florence Joly Lobbedez Session: Poster session 13 2002P - Efficacy and biomarker analysis of neoadjuvant disitamab vedotin combined immunotherapy in patients with muscle-invasive bladder cancer: A multi-center real-world studyPresenter: Luzhe Yan Session: Poster session 13 2003P - Clinical outcomes of patients with metastatic urothelial carcinoma (mUC) discontinuing enfortumab vedotin (EV) monotherapy (mono) without disease progressionPresenter: Michal Sternschuss Session: Poster session 13 2004P - The combination of high levels of serum cytokeratin fragment 21-1 and VI-RADS≧4 has diagnostic and prognostic value in high-stage bladder cancerPresenter: Shunsuke Ikuma Session: Poster session 13 2005P - Prediction of response and identification of mechanisms of resistance to neoadjuvant chemotherapy according to molecular subtypes in muscle-invasive bladder carcinomaPresenter: Alvaro Pinto Marin Session: Poster session 13 2006P - Prognostic factors in metastatic urothelial cancer (mUC): Developing an accessible model for predicting patient survivalPresenter: Sevinc Balli Session: Poster session 13 This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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