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 session1956P - Integrative analysis of 26848 human transcriptomes reveals cancer-defining transcriptional architecture at the isoform resolutionPresenter: Junghoon Shin Session: Poster session 13 1957P - Integrative proteomic profiling in high-grade serous ovarian carcinoma: Unraveling biomarkers and therapeutic targetsPresenter: Ido Wolf Session: Poster session 13 1958P - Influence of androgen deprivation therapy (ADT) on epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features in prostate cancer (PCa)Presenter: Marina Puchinskaya Session: Poster session 13 1968P - Study EV-103 dose escalation/cohort A (DE/A): 5y follow-up of first-line (1L) enfortumab vedotin (EV) + pembrolizumab (P) in cisplatin (CIS)-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC)Presenter: Jonathan Rosenberg Session: Poster session 13 1969P - Phase I/II study of ipilimumab plus nivolumab combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinomaPresenter: Rohit Jain Session: Poster session 13 1972P - Pre-treatment (Tx) risk factors for enfortumab vedotin-induced peripheral neuropathy (EVIPN) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of UNITEPresenter: Amanda Nizam Session: Poster session 13 1973P - Urine-based molecular testing identifies FGFR alteration-positive patients for treatment with TAR-210Presenter: Felix Guerrero-Ramos Session: Poster session 13 1974P - A phase II trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladderPresenter: Guarionex DeCastro Session: Poster session 13 1975P - Avelumab first-line (1L) maintenance in advanced urothelial carcinoma (aUC): Conditional survival and long-term safety in patients (pts) treated for ≥1 or ≥2 years in JAVELIN Bladder 100Presenter: Petros Grivas 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.
|