An updated ASCO guideline recommends lutetium-177–labeled PSMA-617 (LuPSMA), a targeted radioligand therapy, for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who have been treated with one prior line of androgen receptor pathway inhibitor and at least one prior line of chemotherapy.1 In the updated guidance, the ASCO expert panel also recommends positron-emission tomography (PET) imaging with either gallium Ga-68 PSMA-11 or F-18 piflufolastat radiotracer to determine eligibility.
Several new treatments have become available for patients with metastatic castration-resistant prostate cancer in recent years. They include new androgen receptor pathway inhibitors for first-line treatment of metastatic castration-resistant prostate cancer, immunotherapy, and poly (ADP-ribose) polymerase (PARP) inhibitors.2
“[LuPSMA] is a valuable additional option that could help this patient population more broadly than some of these other agents,” said Rohan Garje, MBBS, of the Miami Cancer Institute at Baptist Health South Florida, formerly of the University of Iowa Hospitals & Clinics, and guideline Expert Panel Co-Chair. For example, PARP inhibitors benefit a minority of patients who have DNA repair pathway alterations, whereas the majority of patients with metastatic castration-resistant prostate cancer have PSMA-positive disease and could be eligible for radioligand therapy, Dr. Garje added. Additionally, radium-223, the other systemic radiotherapy for metastatic castration-resistant prostate cancer, is limited to patients with bone metastases, whereas LuPSMA may be an option for patients with bone or visceral organ metastasis.
In March 2022, the U.S. Food and Drug Administration (FDA) approved LuPSMA for the treatment of metastatic castration-resistant prostate cancer, as well as Ga-68 PSMA-11 for detection of PSMA-positive lesions and patient selection, based on the efficacy and safety data from the VISION trial.3 The panel wanted to include F-18 piflufolastat, which was approved by the FDA in 2021 for the detection of metastatic and recurrent prostate cancer, as another option for patient selection, because it is more readily available at several institutions, which have established protocols for working with this radiotracer, Dr. Garje said.4
VISION Data Spur New Treatment Guidance
The new guideline recommendations are based on VISION, an open-label phase III trial of patients with PSMA-positive metastatic castration-resistant prostate cancer who experienced disease progression following at least one androgen receptor pathway inhibitor and one or two taxane regimens.5 The trial randomly assigned 831 patients 2:1 to receive LuPSMA plus protocol-permitted standard care treatments, which included hormonal therapies, or standard care alone.
The median overall survival in VISION was significantly improved in the group that received LuPSMA compared with the standard care–alone group (15.3 vs 11.3 months; hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.52–0.74; P < .001), with a median follow-up of 20.9 months. Grade 3 or higher adverse events were more common in the LuPSMA group (52.7% vs 38.0%), and anemia and fatigue were among the most common in both groups.
“[LuPSMA] is an important tool in our arsenal in treating patients with metastatic prostate cancer and currently helps address an unmet need in this population. At multiple sites in the United States and Europe, a number of patients are being treated with [LuPSMA], so we thought this would be a good time to provide updates to the existing guidelines,” said Rahul A. Parikh, MD, PhD, of the University of Kansas Medical Center, and guideline Expert Panel Co-Chair.
The panel is currently working on complete guidelines for metastatic castration-resistant prostate cancer. It will include all the new agents that have become available since the previous ASCO treatment recommendations for metastatic castration-resistant prostate cancer in 2014.6
“[LuPSMA] is the tip of the iceberg in this new evolving field of theranostics—using radioligand agents to target cancer cells, and prostate cancer is the leading cancer type,” Dr. Garje said. “[LuPSMA] is being evaluated in earlier lines of therapy and in combination with chemotherapy, immunotherapy, and antiandrogens. Additional radioligand agents, such as actinium-225, lead-212, and thorium-227, are also in clinical evaluation,” Dr. Garje added.
1. Garje R, Rumble RB, Parikh RA: Systemic therapy update on 177-lutetium–PSMA-617 for metastatic castration-resistant prostate cancer: ASCO rapid recommendation. J Clin Oncol. September 16, 2022 (early release online).
2. Maluf FC, Pereira FMT, Silva AG, et al: Consensus on the treatment and follow-up for metastatic castration-resistant prostate cancer: A report from the first global prostate cancer consensus conference for developing countries. JCO Glob Oncol 7:559-571, 2021.
3. U.S. Food and Drug Administration: FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer. Accessed October 19, 2022.
4. U.S. Food and Drug Administration: FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer. Available at https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer. Accessed October 19, 2022.
5. Sartor O, de Bono J, Chi KN, et al: Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med 385:1091-1103, 2021.
6. Basch E, Loblaw DA, Oliver TK, et al: Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline. J Clin Oncol 32:3436-3448, 2014.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, September 21, 2022. All rights reserved.