Panagiotis J. Vlachostergios, MD, PhD, and colleagues from Weill Cornell Medical College presented results of their work assessing the association of radiographic measurement of PSMA expression and response to PSMA- targeted radionuclide therapy. Their general clinical mantra for treatment based on PSMA imaging is to not select patients for treatment based upon imaging results. This analysis examined the relationship between imaging and response.
For this study, men with mCRPC had either planar radiolabeled J591 imaging (111In-J591 and/or 177Lu-J591) or 68Ga-PSMA11 PET/CT. Visual scores were assigned based upon PSMA uptake in tumors compared to liver uptake and scored on a 0-4 scale. More specifically, on planar imaging the scores were: 0 (no uptake), 1 (weakly positive), 2 (definitely positive), 3 (equal intensity with the liver), and 4 (greater uptake than the liver). For PET the scores were: 0 (negative), 1 (lesion’s SUVmax < liver SUVmean), 2 (lesion’s SUVmax 1-2.5x liver SUVmean), 3 (lesion’s SUVmax >2.5-5x liver SUVmean) and 4 (lesion’s SUVmax >5x liver SUVmean).
Imaging scores were associated with PSA decline (≥30%, ≥50%) using Cox regression analysis. As several studies were dose-escalation in nature with prior demonstration of dose-response, the investigators controlled for dose administered.
There were 223 men with mCRPC, with a median age of 71.2 years (range (44.6-93.4) and median PSA 73.6 ng/dl (range 0.49-2746). They were treated with PSMA- targeted radionuclide therapy as follows:
- 177Lu-J591 (n=137)
- 177Lu-PSMA-617 (n=44)
- Lu-J591 + Lu-PSMA-617 combination (n=6)
- 225Ac-J591 (n=7)
- 90Y-J591 (n=29).
High PSMA expression was associated with more frequent PSA decline (≥30%: 38.9 vs 16.4% p=0.002; ≥50%: 26.9 vs 7.3% p=0.002). When controlling for dose level, this association remained significant for low (≥30%: 22 vs 5.9% p=0.04) and high doses of radionuclide therapy (≥50%: 36.5 vs 9.5% p=0.02). 13 (6%) patients with no PSMA uptake (VS=0) had PSA declines.
In conclusion, this study notes that it is the first to formally analyze response to PSMA-targeted radionuclide therapy by PSMA imaging expression in an unselected patient population. The level of PSMA expression measured by imaging is associated with the chance of response – patients with low PSMA expression are less likely to respond. However, a subset of patients without any significant PSMA uptake on imaging did demonstrate a response to PSMA-targeted radionuclide therapy, indicating that imaging cannot exclude all patients that might benefit.
Clinical trial information: NCT03545165, NCT03276572, NCT03042468, NCT02552394
Presented by: Panagiotis J. Vlachostergios, MD, PhD, Weill Cornell Medical College & New York-Presbyterian Hospital, New York, NY
Co-Authors: Muhammad Junaid Niaz, Seyed Ali Mosallaie, Paul J. Christos, Amy Hackett, Joseph R. Osborne, Yuliya Jhanwar, Lauren Gracey, Ana M. Molina, David M. Nanus, Neil Harrison Bander, Scott T. Tagawa; Division of Hematology & Medical Oncology, Weill Cornell Medical College & New York-Presbyterian Hospital, New York, NY; Weill Cornell Medical College, New York, NY; Weill Cornell Medicine, Division of Nuclear Medicine, New York, NY; Department of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY; Weill Cornell Medicine/Cornell University, New York, NY; Weill Cornell Medicine, New York, NY; Sandra and Edward Meyer Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA