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 session54P - BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic biliary tract carcinoma (BTC)Presenter: Zhihao Lu Session: Poster session 13 55P - Subsequent anticancer therapy (SAT) analysis from 3-year follow-up of the phase III TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in biliary tract cancer (BTC)Presenter: Arndt Vogel Session: Poster session 13 56P - Multi-omic profiling in cholangiocarcinoma to enable scientific advancement within the DKFZ/NCT/DKTK MASTER studyPresenter: Federico Nichetti Session: Poster session 13 57P - Integrative analysis of the genomic and transcriptomic landscape identifies ciliary genes as a therapeutic target in bile duct cancerPresenter: Pietro Carotenuto Session: Poster session 13 58P - Efficacy and safety of liposomal irinotecan (nal-IRI) plus fluorouracil (5-FU) and leucovorin (LV) versus 5-FU/LV alone for advanced biliary tract cancer (BTC) after progression on gemcitabine-based therapy: A pooled analysis of the NIFTY and NALIRICC trialsPresenter: Changhoon Yoo Session: Poster session 13 59P - Prognostic score to predict recurrence after pancreaticoduodenectomy for ampullary carcinoma: Results from the French prospective FFCD cohortPresenter: Gael Roth Session: Poster session 13 60P - Baseline characteristics and molecular testing of patients with IDH1-mutated cholangiocarcinoma: Initial results from the phase IIIb ProvIDHe studyPresenter: Lorenza Rimassa Session: Poster session 13 61P - Addressing racial disparities in clinical trials in cholangiocarcinomaPresenter: Abhinav Vyas Session: Poster session 13 Resources: Abstract 62TiP - HERIZON-BTC-302: A phase III study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line (1L) treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC)Presenter: Teresa Macarulla Mercade Session: Poster session 13 240P - Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in older patients (pts) with HR+/HER2− early breast cancer (EBC) in NATALEEPresenter: Michael Untch 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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