New Study Shows High Efficacy and Patient Tolerance with 177Lu-PSMA-617 in Older Men with mCRPC

How does ¹⁷⁷Lu-PSMA-617 fare in real-world settings for the treatment in taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC)?

Researchers sought to answer this question in a retrospective study of 500 patients (median age of 75) with mCRPC who were previously treated with one or more androgen receptor pathway inhibitors (ARPIs). The median prostate-specific antigen (PSA) level of the cohort was 26.7 ng/mL and there was a median time of 23.6 months between the diagnosis of mCRPC and initiation of ¹⁷⁷Lu-PSMA-617 (Pluvicto, Novartis), according to the study.

The study findings, presented at the American Society of Clinical Oncology Genitourinary Cancers (ASCO-GU) Symposium in San Francisco, revealed that out of 219 patients with available pre- and post-PSA data, 26 percent had a PSA90 response, 39 percent had a PSA80 response and 63 percent had a PSA50 response. The study authors also noted a median progression-free survival (PFS) of 13.5 months in the cohort.

In an interview with Diagnostic Imaging, study author Daniel George, M.D., said he was surprised by the patient tolerance with ¹⁷⁷Lu-PSMA-617 in an older real-world population with underlying comorbidities.

“ … This is cytotoxic radiotherapy. It is targeted using a PSMA PET scan to identify patients and then using a PSMA targeted radioligand to deliver the therapy. But, nonetheless, this is a whole-body exposure to patients, and many of these patients may have underlying comorbidities. … All of these things, I think could, really mitigate the benefits we see in clinical trials, and yet, we didn't see that, and I think it's remarkable,” maintained Dr. George, co-chair of the DCI Center for Prostate and Urologic Centers, and director of genitourinary oncology at the Duke Cancer Institute in Durham, N.C.

In light of the study findings and what Dr. George referred to as a “wide therapeutic index” for ¹⁷⁷Lu-PSMA-617, he says continued research may reveal combination therapy possibilities with the agent in patients with prostate cancer.

“(This may become) a new standard of care platform to build additional treatments onto, and the fact that is well tolerated in the general prostate cancer population bodes well for future combinations,” posited Dr. George.

(Editor’s note: For related content, see “New PSMA PET Research Shows Merits of Pluvicto in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC),” “Comparative Study Shows Merits of PSMA PET/CT for Local Staging of Intermediate and High-Risk PCa” and “Can PET Imaging Predict Treatment Outcomes for the 225Ac-labeled PSMA Radiopharmaceitical in Patients with mCRPC?”)