At the European Society for Nuclear Medicine Annual Congress, Philip Kuo, MD, PhD, University of Arizona Cancer Center, Tucson, Arizona, presented results from a sub-study of the phase 3 VISION trial. The VISION trial evaluated the addition of [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) to the standard of care among patients with metastatic castration-resistant prostate cancer. This sub-study investigated the association between higher quantitative PSMA expression and response to ¹⁷⁷Lu-PSMA-617 therapy.

Dr Kuo concluded, “Our findings validate the use of visual inspection of PSMA PET scans as a way of selecting patients with PSMA-positive mCRPC as candidates for ¹⁷⁷Lu-PSMA-617 and demonstrates the potential of quantitation of PSMA PET scans for precision oncology.”

Transcript:

Hello, my name is Philip Kuo, and I am a professor of medical imaging, medicine, and biomedical engineering. On behalf of my co-authors, I'm pleased to talk to you about our VISION sub-study, which was just presented in September of this year at EANM, the European Association of Nuclear Medicine annual meeting. We investigated the association of baseline quantitative [⁶⁸Ga]Ga-PSMA-11 (⁶⁸Ga-PSMA-11) PET imaging parameters with clinical outcomes in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving lutetium-PSMA 617 (¹⁷⁷Lu-PSMA-617).

Prostate-specific membrane antigen, or PSMA, is highly expressed on the surface of prostate cancer cells, making it an important and actionable theranostic target. The phase 3 VISION study demonstrated the efficacy and safety of a PSMA-targeted radioligand therapy called ¹⁷⁷Lu-PSMA-617 in patients with heavily-pretreated, progressive. PSMA-positive mCRPC. In the trial, we used the visual inspection of gallium-PSMA-11 (⁶⁸Ga-PSMA-11) PET scans, according to predefined criteria, to identify eligible patients who were randomized to either ¹⁷⁷Lu-PSMA-617 plus protocol-permitted standard of care, or protocol-permitted standard of care only. The aim of our post-hoc study, which was required by the FDA, was to examine the association between the response to ¹⁷⁷Lu-PSMA-617 in the VISION trial and quantitative parameters from segmented disease in the patient's baseline ⁶⁸Ga-PSMA-11 PET scan, specifically the mean radiotracer uptake, known as SUV-mean, as well as SUV-max, PSMA-positive tumor volume, and tumor load. We measured these parameters in the whole-body and in different anatomical regions. Firstly, we made sure that the baseline parameters were similar between the treatment and standard of care arms, which they were. And this allowed us to proceed with the analyses.

We found a linear relationship between increasing whole-body SUV-mean and improved outcomes. Whole-body SUV-mean is the average SUV of all the voxels of segmented disease in all the anatomic regions. Each single unit increase in whole body SUV-mean was associated with a 12% decrease in the risk of progression and 10% decrease in the risk of death. We did not find a definitive cut point value for SUV-mean that separated patients into those who would receive greater or lesser benefit.

Improved radiographic progression-free survival (rPFS) benefit of ¹⁷⁷Lu-PSMA-617 was associated with increasing baseline whole-body SUV-mean quartile. There was an increase in median rPFS of 1.9 months in the lowest quartile and 10.2 months in the highest quartile with a hazard ratio of 0.34 in the highest quartile. Improved overall survival was also associated with increasing baseline whole-body SUV-mean quartile with an increase of 3.2 months in the lowest quartile and 6.4 months in the highest quartile and a hazard ratio of 0.47 in the highest quartile. Overall, we found that patients in all 4 whole-body SUV-mean quartiles benefited in terms of rPFS and overall survival with the addition of ¹⁷⁷Lu-PSMA-617 to the standard of care.

Some of the limitations of our study were that VISION was not designed or powered for PET subgroup analyses. PET scanners and reconstruction parameters differed among the study sites and neither methods nor findings are validated for current clinical practice.

It makes sense that higher SUV-mean could be linked to better efficacy because of higher PSMA expression on the tumor which would enable greater binding and uptake of the targeted radioligand. Our new analysis has shown that the ⁶⁸Ga-PSMA-11 PET read rules using qualitative visual inspection did ensure that every patient's level of PSMA expression was high enough for potential benefit in VISION. Additionally, higher quantitative expression was associated with greater benefit. It is important to point out that quantitative whole-body SUV-mean values are not typically reported in clinical practice.

Our findings validate the use of visual inspection of PSMA PET scans as a way of selecting patients with PSMA-positive mCRPC as candidates for ¹⁷⁷Lu-PSMA-617 and demonstrates the potential of quantitation of PSMA PET scans for precision oncology. Thank you very much.

Source:

Kuo PH, Morris M, Kendi AT, et al. Association of baseline quantitative [68Ga]Ga-PSMA-11 PET imaging parameters with clinical outcomes in patients with mCRPC receiving [177Lu]Lu-PSMA-617: a VISION sub-study. Presented at the EANM Annual Congress; September 9-13, 2023; Vienna, Austria. Abstract OP-340.