PD05-10 TOAD: WARTS AND ALL? SUBGROUP ANALYSES REVEALING DIFFERENTIAL TREATMENT EFFECTS IN THE TIMING OF ANDROGEN DEPRIVATION TRIAL

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I (PD05)1 Sep 2021PD05-10 TOAD: WARTS AND ALL? SUBGROUP ANALYSES REVEALING DIFFERENTIAL TREATMENT EFFECTS IN THE TIMING OF ANDROGEN DEPRIVATION TRIAL Kristian Stensland, Theresa Devasia, Megan Caram, Alexander Zaslavsky, Jordan Sparks, Christina Chapman, Jennifer Burns, Varsha Vedapudi, Gillian Duchesne, Alexander Tsodikov, and Ted Skolarus Kristian StenslandKristian Stensland More articles by this author , Theresa DevasiaTheresa Devasia More articles by this author , Megan CaramMegan Caram More articles by this author , Alexander ZaslavskyAlexander Zaslavsky More articles by this author , Jordan SparksJordan Sparks More articles by this author , Christina ChapmanChristina Chapman More articles by this author , Jennifer BurnsJennifer Burns More articles by this author , Varsha VedapudiVarsha Vedapudi More articles by this author , Gillian DuchesneGillian Duchesne More articles by this author , Alexander TsodikovAlexander Tsodikov More articles by this author , and Ted SkolarusTed Skolarus More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001969.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The TOAD trial (Lancet Oncology 2016) found an overall survival benefit for immediate compared to delayed androgen deprivation therapy (ADT) for PSA-relapsed or non-curable prostate cancer. However, the trial’s broad eligibility criteria allowed entry of a heterogeneous group of participants, including those with prior ADT exposure, raising concerns about subsequent androgen-sensitivity. For these reasons, we conducted sub-group analyses using trial data to assess if prior ADT was associated with the efficacy of ADT timing after PSA relapse. METHODS: We examined TOAD trial patient-level data for participants with PSA relapse after prior definitive local therapy. We performed Kaplan-Meier analyses for overall survival stratified by prior ADT and randomized treatment arm (immediate or delayed ADT). We compared characteristics between subgroups and examined effects of prior ADT on overall survival using multivariable Cox proportional hazards models. RESULTS: We identified 261 patients with PSA-relapse (No prior ADT: 68 delayed, 69 immediate ADT; Prior ADT: 69 delayed, 55 immediate ADT, p=0.40). Patients with prior ADT had slightly higher PSA at presentation (12.05 vs. 9.00, p <0.001), and were more likely to have received radiotherapy as local treatment (79.8% vs 48.2%, p <0.001), but were otherwise similar to patients without prior ADT exposure. Patients with prior ADT who received immediate ADT had better overall survival compared to other groups (p=0.02, Figure 1a). I.e., the benefit of immediate vs. delayed ADT was seen in the prior ADT group (p=0.004, Figure 1b), but not in the no prior ADT group (p=0.82, Figure 1c). This was supported on multivariable analysis, as the only association with overall survival was the immediate treatment X prior ADT interaction term (HR 0.13 [95% CI 0.02-0.73], p=0.02). A similar pattern was found for prostate cancer specific survival. CONCLUSIONS: The overall survival benefit demonstrated in the TOAD trial may be driven by whether patients received ADT prior to trial entry. There are multiple possible explanations for this difference in addition to post-hoc trial selection bias, including issues surrounding potentiation of androgen sensitivity, with significant implications for treatment of relapsed prostate cancer and future study planning. Source of Funding: Dr. Stensland is supported by the National Cancer Institute T32 CA180984. Dr. Skolarus is supported by the National Cancer Institute R01 CA242559 and R37 CA222885 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e59-e60 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kristian Stensland More articles by this author Theresa Devasia More articles by this author Megan Caram More articles by this author Alexander Zaslavsky More articles by this author Jordan Sparks More articles by this author Christina Chapman More articles by this author Jennifer Burns More articles by this author Varsha Vedapudi More articles by this author Gillian Duchesne More articles by this author Alexander Tsodikov More articles by this author Ted Skolarus More articles by this author Expand All Advertisement PDF downloadLoading ...