恩扎鲁胺
前列腺癌
医学
肿瘤科
阿比曲酮
内科学
癌症
生物标志物
醋酸阿比特龙酯
雄激素受体
生物
雄激素剥夺疗法
生物化学
作者
Christopher J. Sweeney,Russell Petry,Chang Xu,Merrida Childress,Jie He,David Fabrizio,Ole Gjoerup,Samantha Morley,Timothy Catlett,Zoe June Assaf,Kobe Yuen,Matthew J. Wongchenko,Kalpit Shah,Pratyush Gupta,Priti S. Hegde,Lincoln Pasquina,Sanjeev Mariathasan,Ryon P. Graf,Peter Schmid
标识
DOI:10.1158/1078-0432.ccr-24-1096
摘要
Abstract Purpose: Enzalutamide after abiraterone progression is commonly used in metastatic castration resistant prostate cancer (mCRPC) despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients more likely to exhibit survival benefit from enzalutamide. Experimental Design: ctDNA was quantified from plasma samples using a tissue-agnostic assay without buffy coat sequencing. Baseline ctDNA TF, changes in ctDNA TF from baseline to cycle 3 day 1 (C3D1), and detection at C3D1 alone, were compared vs overall response rate (ORR), radiographic progression-free survival (rPFS), median OS (mOS), and 50% reduction in PSA. Results: ctDNA TF detection at baseline and/or C3D1 was associated with shorter rPFS and OS in 494 evaluable patients. Detection of ctDNA TF at C3D1, with or without detection at C1D1, was associated with worse rPFS and mOS than lack of detection. When ctDNA TF and PSA response at C3D1 were discordant, patients with [ctDNA TF undetected/PSA not reduced] had more favorable outcomes than [ctDNA TF detected/PSA reduced] (mOS 22.1 months vs. 16 months, p<0.001). Conclusions: In a large cohort of mCRPC patients receiving enzalutamide after abiraterone, we demonstrate the utility of a new tissue-agnostic assay for monitoring molecular response based on ctDNA TF detection and dynamics. CtDNA TF provides a minimally-invasive, complementary biomarker to PSA testing and may refine personalized treatment approaches.
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