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 session2007P - Similar genetic profile in early and late-stage urothelial tract cancer suggests that early genomic testing bears the potential of timely personalized treatment in clinical trialsPresenter: Dag Rune Stormoen Session: Poster session 13 2008P - Assessing response durability and survival after second-line pembrolizumab in advanced urothelial carcinoma: A multicenter validation of a risk modelPresenter: Samer Salah Session: Poster session 13 2010P - Trifunctional anti-EpCAM/CD3 bsAb catumaxomab intravesically for high and intermediate risk non muscle invasive bladder cancer (HMR-NMIBC): Interim analysis of a phase I studyPresenter: Aleksander Antoniewicz Session: Poster session 13 2011P - Neoadjuvant immunotherapy-driven bladder preservation for muscle-invasive bladder cancer: A multicenter, propensity score-matched cohort studyPresenter: Jiao Hu Session: Poster session 13 2012P - Role of first-line immunotherapy in urothelial cancer with bone metastases: A national cancer database analysis of 3971 patientsPresenter: Zin Myint Session: Poster session 13 2013P - First preliminary results of artificial intelligence generated treatment recommendations for urothelial cancer based on multidisciplinary cancer conferences from the KITTU projectPresenter: Gregor Duwe Session: Poster session 13 2014P - Overall survival (OS) results in phase II trial of cabozantinib (CABO) plus durvalumab (DURVA) in patients with urothelial carcinoma (UC) or non-UC variant histologies (VH) after platinum chemotherapy (ARCADIA)Presenter: Patrizia Giannatempo Session: Poster session 13 2015P - Serum nectin-4: Prognostic and predictive value in bladder cancer?Presenter: Kerstin Junker Session: Poster session 13 2017P - Intrinsic molecular difference between bladder and upper tract urothelial carcinomas and its impacts in treatment responsePresenter: Jiwon Kim 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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