(I wasn't sure if the link would work for everyone, so here's the whole press release)
ASCO 2021: VISION Shows Addition of 177Lutetium-Labeled Prostate-Specific Membrane Antigen Improves Outcomes in Advanced Prostate Cancer
Pending regulatory approval, this could become a novel treatment approach
June 6, 2021—177Lutetium-labeled prostate-specific membrane antigen (PSMA) resulted in improvements in both progression-free survival (PFS) and overall survival (OS) when given in combination with standard of care in patients with metastatic castration-resistant prostate cancer (CRPC), according to results of the VISION trial, presented at the annual meeting of the American Society of Clinical Oncology, which took place online from June 4 to 8.
“Prostate cancer is the most common cancer in American men and the second leading cause of cancer-related death,” said lead author Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center in New York City, during a press conference attended by Elsevier’s PracticeUpdate. “Metastatic CRPC is the terminal phase of this disease and has a limited number of effective and durable treatment options. PSMA is an enzyme that is highly expressed on the surface of prostate cancer [cells] across the disease spectrum and across disease sites. Expression on normal tissue is limited, making PSMA an excellent target for both PET imaging and targeted systemic radiation treatment, which is known as radioligand therapy. PSMA-617 targets PSMA with high affinity and delivers a payload of 177lutetium, a beta particle emitting radioactive metal.” Upon uptake of the molecule, the prostate cell is exposed to a lethal dose of radiation and subsequently dies.
The VISION trial was designed to evaluate the efficacy and safety of 177lutetium-labeled PSMA-617 to standard of care in patients with advanced prostate cancer. For the international, open-label, phase III trial, 831 patients with PSMA-positive metastatic CRPC were randomized 2:1 to either 200 mCi of 177lutetium-PSMA-617 for 4 cycles every 6 weeks plus standard of care (n = 551) or standard of care alone (n = 280). All patients had received previous treatment with at least 1 androgen receptor inhibitor and 1 or 2 chemotherapy regimens. “Only patients for whom chemotherapy was felt to be inappropriate were eligible,” said Dr. Morris.
Standard of care was planned before randomization and excluded chemotherapy, immunotherapy, radium-233, and investigational drugs. Responders with residual disease could receive combination treatment for 2 extra cycles. The alternate primary endpoints were radiographic PFS and OS. If either or both of these endpoints were positive, the trial was considered a success.
Treatment with 177lutetium-labeled PSMA resulted in a 38% reduction in risk of death, compared with standard of care alone (95% confidence interval 0.52–0.74, P < .001) and a prolonged median OS (15.3 months vs 11.3 months). A 60% reduction in risk of radiographic progression was also found in the combination arm (95% confidence interval 0.29–0.57), as well as improvement in radiographic PFS, with a median of 8.7 months in the combination arm versus 3.4 months with standard of care alone.
Side effects were more common in the combination arm, with 23.4% experiencing high grade (3–5) bone marrow suppression versus 6.8% of patients treated with standard of care alone. Common side effects of any grade included fatigue (49.1% vs 29.3%), dry mouth (39.3% vs 1.0%), and nausea/vomiting (39.3% vs 17.1%).
“The VISION study demonstrated that patients with metastatic CRPC, who have already progressed after both androgen receptor pathway inhibitors and chemotherapy, had significantly improved OS and radiographic PFS if they received 177lutetium-PSMA in addition to safely combinable standards of care, relative to those standards alone,” concluded Dr. Morris. “These findings do warrant adoption of 177lutetium-PSMA as a new treatment option in this patient population, pending FDA review. There are ongoing studies of patients with prostate cancer at earlier phases of the disease using this agent.”
“This trial shows an alternative to traditional therapies by using radiation targeted to PSMA, so it can be delivered directly to the prostate cancer cells. By doing that, survival was significantly improved,” said Lori J. Pierce, MD, of the University of Michigan in Ann Arbor, at the ASCO press conference. Dr. Pierce spoke in her capacity as ASCO president. “Use of this PSMA radioligand therapy, if it obtains regulatory approval, could indeed become an important treatment option in [these patients].”