Impact of androgen receptor alterations on cell‐free DNA genomic profiling on survival outcomes in metastatic castration‐resistant prostate cancer

• Published in: The Prostate 2023-12, Vol.83 (16), p.1602-1609
• Main Authors: Tripathi, Nishita, Thomas, Vinay Mathew, Sayegh, Nicolas, Gebrael, Georges, Chigarira, Beverly, Jo, Yeonjung, Li, Haoran, Sahu, Kamal K., Nussenzveig, Roberto, Nordblad, Blake, Swami, Umang, Agarwal, Neeraj, Maughan, Benjamin L.
• Format: Article
• Language: English
• Subjects: Androgen receptors; Androgens; Castration; Clinical trials; DNA fingerprinting; Genomics; Metastases; Metastasis; Patients; Prostate cancer; Taxanes
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.24618

BackgroundAndrogen receptor (AR) gene alterations, as detected by circulating tumor cell‐free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration‐resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real‐world patient population of mCRPC experiencing disease progression on an ARPI.MethodsIn this IRB‐approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild‐type (ARwt) or alteration‐positive (AR+). The objective was to correlate overall survival (OS) after disease progression on the first‐line ARPI with the presence or absence of AR alterations. Kaplan–Meier and Cox Regression Tests were used as implemented in R‐Studio (v.4.2).ResultsA total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+. The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p