A novel radiotherapy that targets cells expressing prostate-specific membrane antigen (PSMA) could become an important new treatment option for men with metastatic castration-resistant prostate cancer (mCRPC), investigators reported at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
The radiotherapy, lutetium-177-PSMA-617 (177Lu-PSMA-617), added to the current standard of care (SOC) improved survival outcomes in men whose cancer progressed after prior treatment. The medication binds to PSMA, an enzyme highly expressed on the surface of prostate cancer cells. “PSMA-617 targets PSMA with high affinity and delivers a payload of 177lutetium, a beta-particle-emitting radioactive metal,” lead investigator Michael J. Morris, MD, of Memorial Sloan Kettering Cancer in New York, NY, explained during an ASCO presscast. “When the drug carrying the 177lutetium payload binds to PSMA, the whole molecule is internalized by the cell, and the cell is then exposed to a lethal dose of radiation and dies.”
Dr Morris and his colleagues conducted the phase 3 randomized, open-label VISION trial (ClinicalTrials.gov Identifier: NCT03511664), which enrolled 831 men with PSMA-positive mCRPC who were previously treated with androgen receptor pathway inhibitors and 1 to 2 taxane regimens. Investigators randomly assigned 551 patients to receive 177Lu-PSMA-617 plus standard of care (SOC) and 280 patients to receive SOC alone. The median study follow-up duration was 20.9 months.
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The men who received 177Lu-PSMA-617 plus SOC experienced significantly longer median radiographic progression-free survival (8.7 vs 3.4 months), median overall survival (15.3 vs 11.3 months), and median time to first symptomatic skeletal event (SSE, 11.5 vs 6.8 months) compared with those who received SOC alone, Dr Morris reported. Patients in the radiotherapy-SOC arm had a 60% decreased risk of disease progression, 38% decreased risk of death, and 50% decreased risk of a first SSE compared with the SOC-only arm.
Although patients in the radiotherapy-SOC arm experienced a higher rate of high-grade, treatment-emergent adverse events compared with the SOC arm (52.7% vs 38.0%), the combination of radiotherapy and SOC was well- tolerated, Dr Morris and colleagues reported.
“These findings do warrant adoption of lutetium-PSMA as a new treatment option in this patient population, pending [U.S. Food and Drug Administration] review,” Dr Morris said, adding that 177Lu-PSMA-617 is being studied for use in patients with earlier-stage prostate cancer.
Commenting on the study’s findings, ASCO President Lori J. Pierce, MD, stated, “Use of this PSMA radioligand therapy, if it obtains regulatory approval, could indeed become an important treatment option for these patients with refractory disease.” Ongoing trials are testing the use of 177Lu-PSMA-617 in earlier-stage prostate cancer.
Disclosure: This research was supported by Endocyte, Inc., a Novartis company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Morris MJ, De Bono JS, Chi KN, et al. Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J Clin Oncol. 2021;39:(suppl 15; abstr LBA4). doi:10.1200/JCO.2021.39.15_suppl.LBA4
This article originally appeared on Cancer Therapy Advisor
