학술논문
Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration
Document Type
Article
Author
Zengin, Zeynep B.; Henderson, Nicholas C.; Park, Joseph J.; Ali, Alicia; Nguyen, Charles; Hwang, Clara; Barata, Pedro C.; Bilen, Mehmet A.; Graham, Laura; Mo, George; Kilari, Deepak; Tripathi, Abhishek; Labriola, Matthew; Rothstein, Shoshana; Garje, Rohan; Koshkin, Vadim S.; Patel, Vaibhav G.; Schweizer, Michael T.; Armstrong, Andrew J.; McKay, Rana R.; Alva, Ajjai; Dorff, Tanya
Source
Prostate Cancer and Prostatic Diseases; 20240101, Issue: Preprints p1-7, 7p
Subject
Language
ISSN
13657852; 14765608
Abstract
Background: ARgene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear. Methods: Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types. Results: In total, 540 CRPC patients who received ARTA and had tissue-based (n= 321) and/or blood-based (n= 244) genomic sequencing were identified. Median age was 62 years (range 39−90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and ARmutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with ARamplifications (25.7 months) compared to those without an ARalteration (9.6 months; p= 0.03). In the post-ARTA group (n= 406), ARmutations and ARamplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H(9.9%). Conclusion: In this real-world clinicogenomics database-driven study we explored the development of ARalterations and their association with ARTA treatment outcomes. Our study showed that ARamplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with ARalterations.