Guidelines published for 177Lu-PSMA-617 patient selection and use in prostate cancer

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) has published recommendations for patient selection and appropriate use of the radionuclide therapy ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan; Pluvicto) in patients with prostate cancer.^1,2

“With the approval of 177Lu-PSMA-617, a new class of therapeutics is available to patients with prostate cancer. We look forward to the potential use of PSMA radionuclide therapy in pre-chemotherapy mCRPC or other settings pending the full results of ongoing trials,” the authors noted in their publication.”^1,2

¹⁷⁷Lu-PSMA-617 is approved by the FDA for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with taxane-based chemotherapy and at least 1 line of an androgen receptor pathway inhibitor (ARPI).³

The SNMMI consensus statement on ¹⁷⁷Lu-PSMA-617 patient selection and appropriate use was developed by an autonomous workgroup with multidisciplinary expertise. The workgroup developed their recommendations after reviewing 4 trials of ¹⁷⁷Lu-PSMA-617: the phase 3 VISION trial, the phase 2 TheraP trial, and 2 prospective phase 2 trials that have been published.^1,2

The following are highlights of the patient selection and use criteria developed by the workgroup members:

• PSMA-PET imaging for patient selection should be done “within 3 months of treatment or since progression on the last therapy”
• ⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL are appropriate tools for PSMA-PET imaging
• It is not required that ¹⁸F-FDG PET imaging be a standard component of patient selection
• PSMA-PET imaging should be repeated if there is evidence of either disease progression or intervening therapy
• In order to identify any PSMA-negative disease, patient imaging with contrast-enhanced CT or MRI should be performed
• In line with the FDA-approved indication for ¹⁷⁷Lu-PSMA-617, the workgroup underscored that treating patients with mCRPC after chemotherapy and ARPI is “appropriate,” while treatment of these patients post-ARPI but before chemotherapy is “rarely appropriate.” Also “rarely appropriate,” according to the workgroup, is use of ¹⁷⁷Lu-PSMA-617 in patients with metastatic castration-sensitive disease.^1,2

The full consensus statement, which expands on these criteria and addresses clinical challenges with the use of ¹⁷⁷Lu-PSMA-617 in practice, can be accessed here.

“With the approval of ¹⁷⁷Lu-PSMA-617, a new class of therapeutics is available to patients with prostate cancer. We look forward to the potential use of PSMA radionuclide therapy in pre-chemotherapy mCRPC or other settings pending the full results of ongoing trials,” the authors noted in their publication.”^1,2

Data supporting FDA approval of ¹⁷⁷Lu-PSMA-617

The approval of 177Lu-PSMA-617 was primarily based on findings from the phase 3 VISION trial. The open-label VISION trial (NCT03511664) included 831 patients with progressive PSMA-positive mCRPC who received at least 1 novel androgen axis drug (eg, enzalutamide [Xtandi] or abiraterone acetate [Zytiga]) and were previously treated with 1 to 2 taxane regimens. Patients were randomized in a 2:1 ratio to ¹⁷⁷Lu-PSMA-617 plus SOC (n = 551) or SOC alone (n = 280).⁴

The results showed that adding ¹⁷⁷Lu-PSMA-617 to SOC led to a nearly 40% reduction in the risk of death versus SOC alone. Specifically, the addition of ¹⁷⁷Lu-PSMA-617 improved the median overall survival by 4 months over SOC alone at 15.3 vs 11.3 months, respectively (HR, 0.62; P value < .001).⁴

References

1. JNM Publishes Consensus Statement on Patient Selection and Appropriate Use of Lu-177 PSMA-617 Radionuclide Therapy. Published online September 1, 2023. Accessed September 6, 2023. https://www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=44457

2. Hope TA, Antonarakis ES, Bodei L, et al. SNMMI Consensus Statement on Patient Selection and Appropriate Use of 177Lu-PSMA-617 Radionuclide Therapy. Nucl Med. 2023;64(9):1417-1423. doi: 10.2967/jnumed.123.265952

3. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Published online March 23, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer

4. Highlights of Prescribing Information for Pluvicto® (lutetium Lu 177 vipivotide tetraxetan) injection, for intravenous use. Initial U.S. Approval: 2022. https://www.novartis.com/us-en/sites/novartis_us/files/pluvicto.pdf