Abstract 275P
Background
In 2022, the U.S. Food and Drug Administration (FDA) approved Lutetium-177 Prostate-specific membrane antigen (Lu-177 PSMA). This approval was based on the VISION trial, in which Lu-177 PSMA demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard therapy alone. PSMA is more strongly expressed in prostate cancer than in benign prostatic hyperplasia and correlates with Gleason Score and cancer grade. PSMA is involved in tumor growth by activating IP3K-AKT-mTOR signaling through folate metabolism. PSMA expression is suppressed by androgen receptor (AR) bound complexes with testosterone and promoted by unbound AR. In other words, inhibition of AR signaling enhances PSMA expression. These findings suggest that PSMA is involved in the mechanism of resistance to treatment in castration resistant prostate cancer (CRPC). Our previous study also showed that CRPC patients with PSMA expression in the blood circulating tumor cells (CTCs) have a shorter PFS. In this study, we aimed to determine the association between PSMA expression in CTCs and OS after the initiation of taxane-based chemotherapies in metastatic CRPC.
Methods
Forty-eight patients with metastatic CRPC treated with docetaxel followed by cabazitaxel were included in the study. PSMA expression in CTCs was analyzed over time, and the association between PSMA expression and OS was analyzed.
Results
Twenty-seven patients were positive for PSMA expression, and 21 patients were negative for PSMA expression in CTC. The analysis comparing patient backgrounds showed no significant differences with respect to Gleason Score, number of docetaxel treatments, prior ARATs administration, or metastatic site. On the other hand, patients with positive PSMA showed a longer time to acquire castration resistance. The log-rank test result showed shorter OS after initiation of docetaxel treatment in patients with positive PSMA than in those with negative PSMA (median survival at observation, PSMA-positive group: 618 days; PSMA-negative group: 1187 days; P=0.05).
Conclusions
The expression of PSMA in CTCs was associated with OS after initiation of taxane-based chemotherapy in metastatic CRPC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
602P - COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib (Enco) + binimetinib (Bini) vs vemurafenib (Vemu) or Enco in patients (Pts) with BRAF V600-mutant melanoma
Presenter: Andrew Haydon
Session: Poster Display
Resources:
Abstract
603P - An individualised postoperative radiological surveillance schedule for IDH-wildtype glioblastoma patients (HK-GBM Registry)
Presenter: Jason Chak Yan Li
Session: Poster Display
Resources:
Abstract
604P - Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who progressed after prior VEGFR-targeted therapy: Outcomes from COSMIC-311 by BRAF status
Presenter: Marcia Brose
Session: Poster Display
Resources:
Abstract
606P - BRAF and NRAS mutations are associated with poor prognosis in Asians with acral-lentiginous and nodular cutaneous melanoma
Presenter: Sumadi Lukman Anwar
Session: Poster Display
Resources:
Abstract
607P - Single institutional outcomes of radiotherapy and systemic therapy for melanoma brain metastases in Japan
Presenter: Naoya Yamazaki
Session: Poster Display
Resources:
Abstract
608P - The efficacy of immune checkpoint inhibitors and targeted therapy in mucosal melanomas: A systematic review and meta-analysis
Presenter: Andrea Teo
Session: Poster Display
Resources:
Abstract
609P - The association between thyroid function abnormalities and vitiligo induced by pembrolizumab regarding prognosis in patients with advanced melanoma
Presenter: Moez Mobarek
Session: Poster Display
Resources:
Abstract
610P - Analyzing the clinical benefit of the evidence presented at these congresses and utilizing a standardized scale to quantify it will significantly enhance our understanding of the studies showcased, allowing for more objective evaluation and interpretation
Presenter: Charles Jeffrey Tan
Session: Poster Display
Resources:
Abstract
611P - ESMO-magnitude of clinical benefit scale (MCBS) scores for phase III trials of adjuvant and curative therapies at the 2022 ASCO annual meeting (ASCO22)
Presenter: Thi Thao Vi Luong
Session: Poster Display
Resources:
Abstract
612P - Is the juice worth the squeeze? Overall survival gain per unit treatment time as a metric of clinical benefit of systemic treatment in incurable cancers
Presenter: Vodathi Bamunuarachchi
Session: Poster Display
Resources:
Abstract