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 session252P - Evolution of breast cancer biological subtypes between pre-treatment biopsy and residual disease after neoadjuvant therapyPresenter: Katarzyna Pogoda Session: Poster session 13 253P - Single-cell RNA sequencing reveals tumor heterogeneity and potential mechanisms of response/resistance in breast cancer treated with neoadjuvant therapyPresenter: Marcela Carausu Session: Poster session 13 254P - IHC and GEX biomarkers and their prognostic and treatment predictive role in the neoadjuvant treatment of breast cancerPresenter: Hani Saghir Session: Poster session 13 255P - Predicting early recurrence in breast cancer patients undergoing neo-adjuvant chemotherapy through MRI-radiomics analysisPresenter: Anna D'Angelo Session: Poster session 13 256P - Protein signature of tertiary lymphoid structure predicts efficacy of neoadjuvant chemotherapy in triple-negative breast cancerPresenter: Shuling Zhou Session: Poster session 13 257P - Spatial predictors of pathologic complete response to neoadjuvant chemotherapy using imaging mass cytometry in the IMMUcan TNBC cohortPresenter: Andrea Joaquin Garcia Session: Poster session 13 258P - Correlation between pathological complete response (pCR) following neoadjuvant docetaxel, carboplatin and trastuzumab (TCH) with or without pertuzumab (TCHP) and PAM50 subtypes in HER2(+) early breast cancer (eBC)Presenter: Coralia Bueno Muiño Session: Poster session 13 1954P - 5-methylthioadenosine phosphorylase (MTAP) loss in clinically advanced uveal melanoma (CAUM): A comprehensive genomic profiling (CGP) studyPresenter: Nimisha Srivastava Session: Poster session 13 1955P - Glycan-programmed T cell immunity: Effective adoptive T cell transfer in a CRC preclinical modelPresenter: Yong Miao 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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