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 session1978P - Accurate detection of urothelial carcinoma by whole-genome methylation profiling of urinary cell-free DNAPresenter: Huiqin Guo Session: Poster session 13 1979P - Disitamab vedotin (DV) plus toripalimab (T) in unresectable locally advanced or metastatic urothelial carcinoma (la/mUC): Long-term outcomes from a phase Ib/II studyPresenter: Li Zhou Session: Poster session 13 1980P - Association of PD-L1 expression with clinical response to TAR-200 in the phase IIb SunRISe-1 trialPresenter: Evanguelos Xylinas Session: Poster session 13 1981P - Cabozantinib plus durvalumab in patients with advanced and chemotherapy-treated urothelial carcinoma (UC) and variant histology (VH): An open-label, phase II, single-arm proof-of-concept trial: ARCADIA study. Subgroup analysis for bone metastasisPresenter: Marco Stellato Session: Poster session 13 1982P - Post hoc analysis of outcomes according to prior chemotherapy (CT) response and platinum agent in the international SAUL study of atezolizumab (atezo) for urinary tract carcinoma (UTC)Presenter: Begona Perez Valderrama Session: Poster session 13 1983P - Feasibility and efficacy of split-dose cisplatin with atezolizumab for cisplatin-ineligible urothelial carcinoma (SOGUG-AUREA): Final resultsPresenter: Guillermo Antonio De Velasco Oria Session: Poster session 13 1984P - Efficacy and safety of disitamab vedotin combined with gemcitabine as neoadjuvant therapy for muscle-invasive bladder cancer: A multi-center, single-arm, phase II trialPresenter: Chu Yang Session: Poster session 13 1985P - Retrospective database analysis of real-world treatment patterns and sequencing in locally advanced or metastatic urothelial carcinoma patients receiving sacituzumab govitecanPresenter: Ronac Mamtani Session: Poster session 13 1986P - Prospective evaluation of BCG unresponsive bladder cancer carcinoma in situ identifies genetic mechanisms of immunotherapy resistance and targeted therapy using an ultra-sensitive next generation sequencing minimal residual disease (MRD) assayPresenter: Joshua Meeks 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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