Phillip H. Kuo, MD, PhD, Examines Utility of PSMA-PET Parameters to Predict Response to 177Lu-PSMA-617 in mCRPC

CancerNetwork^® spoke with Phillip H. Kuo, MD, PhD, professor of medical imaging, biomedical engineering, and medicine as well as member of the Graduate Faculty at The University of Arizona College of Medicine in Tucson, at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting where he reviewed the results of a substudy from the phase 3 VISION trial (NCT03511664) which examined use of 177Lu-PSMA-617 (Pluctivo) in patients with pretreated metastatic castration-resistant prostate cancer. Kuo highlighted the need to find an association between prostate-specific membrane antigen (PSMA)–PET imaging and treatment outcomes.¹

In previously reported results for those in the intent-to-treat population who were treated with 177Lu-PSMA-617 plus standard of care (SOC), the median overall survival was 15.3 months vs 11.3 months for SOC alone.² In the substudy, Kuo and colleagues demonstrated that across all standardized uptake value (SUV) mean quartiles by 68Ga-PSMA-11 PET/CT imaging, OS was consistently better with 177Lu-PSMA-617 vs SOC alone.

Transcript:

The PMSA-PET imaging that was done for the trial was for patient selection. Patients received a PSMA-PET scan and then they were read according to these novel criteria that had not been tested in any trial before. In these criteria, which use PSMA-PET and diagnostic CT, we wanted to ensure that there was enough PSMA target expression so these patients would most likely benefit from therapy. If they read out as PMSA positive, which by our threshold means activity on the PET scan greater than the liver, then they went on to be randomized to either standard of care alone, which was the control arm, or standard of care plus 177Lu-PSMA- 617 active compound. If you had even 1 lesion that was PSMA negative, which means activity visually the same as or less than liver, you were then excluded from the trial and not randomized.

In this retrospective substudy, we were asked by the FDA to quantitatively analyze these baseline scans that were initially just used for randomization, whether you’re going to get into the randomized treatment arm or SOC. We knew, or at least we suspected, that there was going to be far more additional prognostic information that we could get from those scans. We quantified the scans in the treatment arm and studied them. We correlated the quantitative parameters from these PSMA-PET scans with the prognostic outcomes to get that correlation. The most important finding, in my opinion, was the parameter SUV mean, SUV being the standardized uptake value. It’s the measure of the activity within a single voxel, which is a 3D pixel within your image. Many oncologists are familiar with the term SUV max, which is the single hottest voxel that is segmented. The mean is the average, so within the entire segmented volume of your PSMA-positive disease, we took the average of all the activity. It gives you a good overall general assessment of the level of PSMA expression of the tumors throughout the whole body. We then separated those by quartile and in the highest quartile of patients with the highest SUV mean, the overall survival was 21 months. Now how does that compare?

Overall in the trial, the median overall survival was 15.3 months, so we had almost a 6-month greater overall survival in the patient population that had the top quartile SUV mean. In the other quartiles—the second, third, and fourth—had ranges of overall survival between 12.6 months and 14.6 months, which is less than the 21 months, but also still better than the standard of care alone arm, which was 11.3 months. Even the lowest quartile of the SUV means still showed benefits over the standard of care alone.

References

1. Kuo P, Hesterman J, Rahbar K, et al. [68Ga]Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [177Lu]Lu-PSMA-617 in patients with mCRPC: A VISION substudy. J Clin Oncol. 2022;40(suppl 16):5002. doi:10.1200/JCO.2022.40.16_suppl.5002
2. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322