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Cancer Discovery Jan 2024Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing...
UNLABELLED
Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
SIGNIFICANCE
Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Nolan-Stevaux et al., p. 90. This article is featured in Selected Articles from This Issue, p. 5.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Immunotherapy; Treatment Outcome; Antigens, Neoplasm; Oxidoreductases
PubMed: 37861461
DOI: 10.1158/2159-8290.CD-23-0964 -
PET Clinics Jul 2024Since its clinical introduction in May 2011, prostate-specific membrane antigen (PSMA)-PET/computed tomography has quickly gained worldwide recognition as a significant... (Review)
Review
Since its clinical introduction in May 2011, prostate-specific membrane antigen (PSMA)-PET/computed tomography has quickly gained worldwide recognition as a significant breakthrough in prostate cancer diagnostics. In the meantime, several new PSMA radioligands for PET imaging have been introduced into routine clinical practice. This article aims to introduce the most commonly used tracers and their key areas of application.
Topics: Humans; Male; Prostatic Neoplasms; Positron Emission Tomography Computed Tomography; Glutamate Carboxypeptidase II; Antigens, Surface; Radiopharmaceuticals; Prostate-Specific Antigen; Prostate
PubMed: 38702228
DOI: 10.1016/j.cpet.2024.03.001 -
Current Urology Reports Oct 2023Many prostate cancer active surveillance protocols mandate serial monitoring at defined intervals, including but certainly not limited to serum PSA (often every... (Review)
Review
PURPOSE OF REVIEW
Many prostate cancer active surveillance protocols mandate serial monitoring at defined intervals, including but certainly not limited to serum PSA (often every 6 months), clinic visits, prostate multiparametric MRI, and repeat prostate biopsies. The purpose of this article is to evaluate whether current protocols result in excessive testing of patients on active surveillance.
RECENT FINDINGS
Multiple studies have been published in the past several years evaluating the utility of multiparametric MRI, serum biomarkers, and serial prostate biopsy for men on active surveillance. While MRI and serum biomarkers have promise with risk stratification, no studies have demonstrated that periodic prostate biopsy can be safely omitted in active surveillance. Active surveillance for prostate cancer is too active for some men with seemingly low-risk cancer. The use of multiple prostate MRIs or additional biomarkers do not always add to the prediction of higher-grade disease on surveillance biopsy.
Topics: Male; Humans; Prostate-Specific Antigen; Watchful Waiting; Prostatic Neoplasms; Biopsy; Prostate; Magnetic Resonance Imaging
PubMed: 37436691
DOI: 10.1007/s11934-023-01177-2 -
BMC Geriatrics Sep 2023Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate...
BACKGROUND
Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate cancer (PCa) remains controversial. Although alcohol is included in DII as a dietary factor, the various adverse health effects of alcohol consumption are not only related to inflammation. On the other hand, it has been a long-standing debate whether alcohol consumption is linked to the risk of PCa. Therefore, to clarify whether drinking affects the relationship between DII and PCa, we evaluated the correlation between DII and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database.
METHODS
We used data from the NHANES spanning from 2005 to 2010 to analyze the relationship between PCa and DII. Out of the 31,034 NHANES participants, we enrolled 4,120 individuals in our study, utilizing dietary intake data from a twenty-four-hour period to determine DII scores. Demographic data, physical and laboratory test results were collected to compare between low PSA and high PSA groups, and to calculate the odds ratio between both groups, we employed a logistic regression analysis.
RESULTS
In this cross-sectional investigation of PCa, drinkers and non-drinkers had different relationships between DII and PSA levels (OR: 1.2, 95% Cl: 1-1.44 vs. OR: 0.98, 95% Cl: 0.9-1.07), and DII and abstaining from alcohol were effective in reducing the incidence of PSA (p-value for significant interaction = 0.037).
CONCLUSION
The results of our study suggest that drinking may influence the relationship between DII and PSA levels. DII is likely to be a reliable indicator for estimating PSA levels among non-drinkers, who may limit their intake of pro-inflammatory ingredients to lower the incidence and death of PCa.
Topics: Male; Humans; Prostate-Specific Antigen; Cross-Sectional Studies; Nutrition Surveys; Diet; Ethanol; Drug-Related Side Effects and Adverse Reactions
PubMed: 37670257
DOI: 10.1186/s12877-023-04151-2 -
Seminars in Nuclear Medicine Jan 2024Prostate cancer (PC) is a significant health concern worldwide, with high incidence and mortality rates. Early and accurate detection and localization of recurrent... (Review)
Review
Prostate cancer (PC) is a significant health concern worldwide, with high incidence and mortality rates. Early and accurate detection and localization of recurrent disease at biochemical recurrence (BCR) is critical for guiding subsequent therapeutic decisions and improving patient outcomes. At BCR, conventional imaging consisting of CT, MRI, and bone scintigraphy are recommended by US and European guidelines, however, these modalities all bear certain limitations in detecting metastatic disease, particularly in low-volume relapse at low prostate-specific antigen (PSA) levels. Molecular imaging with PET/CT or PET/MRI using prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals has revolutionized imaging of PC. Particularly at BCR PC, PSMA PET has shown better diagnostic performance compared to conventional imaging in detecting local relapse and metastases, even at very low PSA levels. The most recent version of the National Comprehensive Cancer Network (NCCN) guideline has included PSMA-targeted PET/CT or PET/MRI for the localization of BCR PC. There are several different PSMA-targeting radiopharmaceuticals labeled with different radioisotopes, each with slightly different characteristics, but overall similar high sensitivity and specificity for PC. PSMA-targeted PET has the potential to significantly impact patient care by guiding personalized treatment decisions and thus improving outcomes in BCR PC patients.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Gallium Radioisotopes; Radiopharmaceuticals; Neoplasm Recurrence, Local; Prostatic Neoplasms; Positron-Emission Tomography; Recurrence
PubMed: 37567795
DOI: 10.1053/j.semnuclmed.2023.07.002 -
Molecular Diagnosis & Therapy Sep 2023Flotufolastat F 18 (POSLUMA) is an F-labelled radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted imaging agent being developed by Blue Earth... (Review)
Review
Flotufolastat F 18 (POSLUMA) is an F-labelled radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted imaging agent being developed by Blue Earth Diagnostics, a subsidiary of Bracco Imaging, for prostate cancer imaging. In May 2023, flotufolastat F 18 received its first approval in the USA as a radioactive diagnostic agent for positron emission tomography (PET) of PSMA positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. This article summarizes the milestones in the development of flotufolastat F 18 leading to this first approval.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Prostate-Specific Antigen; Neoplasm Recurrence, Local
PubMed: 37439946
DOI: 10.1007/s40291-023-00665-y -
European Urology Mar 2024Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in most prostate cancers and exploited as a target for PSMA-targeted therapies.... (Review)
Review
CONTEXT
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in most prostate cancers and exploited as a target for PSMA-targeted therapies. Different approaches to target PSMA-expressing cancer cells have been developed, showing promising results in clinical trials.
OBJECTIVE
To discuss the regulation of PSMA expression and the main PSMA-targeted therapeutic concepts illustrating their clinical development and rationalizing combination approaches with examples.
EVIDENCE ACQUISITION
We performed a detailed literature search using PubMed and reviewed the American Society of Clinical Oncology and European Society of Medical Oncology annual meeting abstracts up to September 2023.
EVIDENCE SYNTHESIS
We present an overarching description of the different strategies to target PSMA. The outcomes of PSMA-targeted therapies strongly rely on surface-bound PSMA expression. However, PSMA heterogeneity at different levels (interpatient and inter/intratumoral) limits the efficacy of PSMA-targeted therapies. We highlight the molecular mechanisms governing PSMA regulation, the understanding of which is crucial to designing therapeutic strategies aimed at upregulating PSMA expression. Thus far, homeobox B13 (HOXB13) and androgen receptor (AR) have emerged as critical transcription factors positively and negatively regulating PSMA expression, respectively. Furthermore, epigenetic regulation of PSMA has been also reported recently. In addition, many established therapeutic approaches harbor the potential to upregulate PSMA levels as well as potentiate DNA damage mediated by current radioligands.
CONCLUSIONS
PSMA-targeted therapies are rapidly advancing, but their efficacy is strongly limited by the heterogeneous expression of the target. A thorough comprehension of how PSMA is regulated will help improve the outcomes through increasing PSMA expression and will provide the basis for synergistic combination therapies.
PATIENT SUMMARY
Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate cancers. PSMA-targeted therapies have shown promising results, but the heterogeneous expression of PSMA limits their efficacy. We propose to better elucidate the regulation of PSMA expression to increase the levels of the target and improve the therapeutic outcomes.
Topics: Male; Humans; Prostate; Epigenesis, Genetic; Prostatic Neoplasms; Antigens, Surface; Prostate-Specific Antigen; Treatment Outcome
PubMed: 38104015
DOI: 10.1016/j.eururo.2023.11.018 -
Investigative and Clinical Urology Sep 2023
Topics: Male; Humans; Prostate-Specific Antigen; Early Detection of Cancer; Prostatic Neoplasms
PubMed: 37668197
DOI: 10.4111/icu.20230229 -
Cancer Jan 2024
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen
PubMed: 37927174
DOI: 10.1002/cncr.35032 -
Tidsskrift For Den Norske Laegeforening... Sep 2023
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 37668127
DOI: 10.4045/tidsskr.23.0530