PSMA heterogeneity analysis in patients with metastatic castrate-resistant prostate cancer (mCRPC): Imaging versus CTCs

Autor: Daniel P. Petrylak, Michael J. Morris, A. Oliver Sartor, Nicholas J. Vogelzang, Mark Landers, Michael S. Gordon, Adam Robarts, Anthony W. Tolcher, Michael Groaning, Phillip H. Kuo, Yipeng Wang, Adam Jendrisak, Richard A. Messmann, Megan Kearney, Hani M. Babiker, Alison Armour
Rok vydání: 2018
Předmět:
Zdroj: Journal of Clinical Oncology. 36:272-272
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2018.36.6_suppl.272
Popis: 272 Background: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, making it an ideal imaging and therapeutic target of interest. The utility of the PSMA-targeted imaging agent 99mTc-EC0652 is being evaluated, along with biomarker analysis of circulating tumor cells (CTCs), in pts with mCRPC in a PSMA-targeted chemotherapeutic study. We now report the PSMA heterogeneity via CTC vs. imaging in the pt population treated to date. Methods: Patients were enrolled in 1 of 2 cohorts: mCRPC taxane naïve or taxane exposed. A total of 48 pts evaluated at the time of the data cut had baseline CT & bone scans performed in addition to a 99mTc-EC0652 SPECT/CT as a measure of imaging-based PSMA expression. 40 of 48 pts provided pre-treatment blood samples evaluable for CTC biomarker analysis, which included PSMA expression & were given percent homologous recombination deficiency (%HRD) scores. Four of the best and four of the worst responders were evaluated in more detail for imaging and CTC-based biomarker analysis as it related to clinical outcome. Results: 35 of 40 pts (88%) had detectable CTCs in their samples. 15 of the 35 (43%) pts had PSMA-positive CTCs. The 4 “non-responders” were on study for an average of 41 days and the 4 “responders” for an average of 256 days. Each group contained 2 taxane exposed & 2 taxane naïve patients. Of the 335 bone lesions analyzed by MDP, CT, 99mTc-EC0652, 333 (99.4%) were characterized as PSMApos based on their 99mTc-EC0652 SPECT/CT scan. Of the 26 soft tissue lesions analyzed by CT, all were characterized as PSMApos based on their 99mTc-EC0652 SPECT/CT scan. Seven (26.9%) of those lesions were CT positive (observed on CT scan). Each group had 2 pts that were CTC-based PSMApos & 2 that were PSMAneg. Their percent homologous recombination deficiency (%HRD) scores were of 0.60 [0.333, 1.0] for “non-responders” & 0.01 [0.0, 0.039] for “responders”. Conclusions: PSMA-based imaging showed a high percentage of positive lesions whereas CTC-based PMSA positivity is lower by comparison (43%). The discordance between the imaging results & CTC-based biomarkers, & the relative therapeutic predictive value, requires additional exploration. Clinical trial information: NCT02202447.
Databáze: OpenAIRE
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