Low/No PSMA Expressing mCRPC Tumors Respond Poorly to 177Lu-PSMA-617 Therapy

Article

Treatment with 177Lu-PSMA-617 resulted in poor outcomes for patients with metastatic castration-resistant prostate cancer whose tumors had little to no prostate-specific membrane antigen expression.

Patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors had low or no prostate-specific membrane antigen (PSMA) expression experienced poor responses following treatment with 177Lu-PSMA-617 therapy, according to findings from a multicenter retrospective analysis presented at the 2022 Society of Nuclear Medicine & Molecular Imaging Annual Meeting.

Baseline PSMA-PET/CT scans were assessed by 1 reader who applied PET criteria from the phase 3 VISION trial (NCT03511664) and determine whether scans were eligible (VISION-PET-E) or a screening failure (VISION-PET-SF).

VISION-PET-SF criteria were defined by the following:

  • Lack of metastatic lesion with an uptake greater than the liver background, denoting low PSMA expression
  • Evidence of 1 or more metastatic measurable lesions
  • Solid/visceral organ lesions

Moreover, VISION-PET-E criteria included the following:

  • 1 or more PSMA-positive metastatic lesions
  • No PSMA-negative metastatic lesions, including bone with soft tissue component (1.0 cm or more), lymph node (2.5 cm or more), and solid organ (1.0 cm or more)

In the VISION-PET-SF population, investigators reported that PSA–progression-free survival (PSA-PFS) was shorter, and poorer outcomes were all noted for PSA responses and overall survival (OS). In particular, the median PSA-PFS was 4.1 months in the VISION-PET-E arm vs 2.1 months in the VISION-PET-SF arm (HR, 1.6; 95% CI, 1.1-2.5; P = .025; log-rank P-value = .023). Moreover, the median OS was 14.2 months compared with 9.6 months in the VISION-PET-E arm and VISION-PET-SF arm, respectively (HR, 1.4; 95% CI, 0.89-2.3; P = .16; log-rank P-value = .16).

Any PSA decline was noted in 71.3% of patients in the VISION-PET-E arm vs 41.4% in the VISION-PET-SF arm (P = .003). Moreover, a PSA decline of 50% or more was reported in 50.3% and 20.7% of patients in either respective arms (P = .005).

A total of 304 patients with mCRPC were included in the analysis who had received 1 or more cycles of 177Lu-PSMA-617. Of these patients, 3 were excluded due to being lost to follow-up (n = 2) or missing a CT image (n = 1). From there, patients were assessed based on VISION PET criteria, of whom 272 were VISION-PET-E and 29 were VISION-PET-SF.

Outcomes included PSA-PFS, OS, PSA decline of 50% or more, and any PSA decline.

Notably, the cohort did not include pre-excluded patients via local site evaluation. Due to this, approximately 20% to 25% of patients in the unselected group would likely have failed screening via VISION PET criteria.

Reference

Hotta M, Gafita A, Czernin J, et al. Outcome of patients with PSMA-PET/CT screen failure by VISION criteria and treated with 177Lu-PSMA therapy: a multicenter retrospective analysis. 2022 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 11-14; Vancouver, BC, Canada; abstract 3039.

Related Videos
Rohit Gosain, MD; Rahul Gosain, MD; and Rana R. McKay, MD, presenting slides
Rohit Gosain, MD; Rahul Gosain, MD; and Rana R. McKay, MD, presenting slides
Rohit Gosain, MD; Rahul Gosain, MD; and Rana R. McKay, MD, presenting slides
Rohit Gosain, MD; Rahul Gosain, MD; and Rana R. McKay, MD, presenting slides
Anemia in patients who receive talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer appears to be manageable without any compromises in patient-reported outcomes and quality of life.
Artificial intelligence models may be “seamlessly incorporated” into clinical workflow in the management of prostate cancer, says Eric Li, MD.
Robust genetic testing guidelines in the prostate cancer space must be supported by strong clinical research before they can be properly implemented, says William J. Catalona, MD.
Financial constraints and a lack of education among some patients and providers must be addressed to improve the real-world use of certain prostate cancer therapies, says Neeraj Agarwal, MD.
Novel anti-PSMA monoclonal antibody rosopatamab is capable of carrying a bigger payload of radiation particles, which may potentially reduce doses for patients with prostate cancer, says Neeraj Agarwal, MD.
Related Content