Targeted Radioligand Therapy Shows Efficacy in PSMA-Positive mCRPC

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EP: 1.Targeted Radioligand Therapy Shows Efficacy in PSMA-Positive mCRPC

EP: 2.Expert Discusses When to Perform PSMA PET Imaging for Metastatic CRPC

Michael J. Morris, MD, prostate cancer section head for genitourinary oncology at Memorial Sloan Kettering Cancer Center, discusses the results of the VISION trial (NCT03511664) of ¹⁷⁷lutetium-PSMA-617 (Pluvicto) in patients with metastatic castration-resistant prostate cancer (mCRPC).

The phase 3 VISION trial randomly assigned patients with mCRPC who were prostate-specific membrane antigen (PSMA)-positive 2:1 to receive best supportive care/standard-of-care therapy with or without ¹⁷⁷lutetium-PSMA-617 once every 6 weeks for 6 cycles. Patients had previously been treated with 1 or 2 taxane-based regimens and androgen-receptor targeted therapy. The primary end points were radiographic progression-free survival (rPFS) and overall survival (OS).

Those who received ¹⁷⁷lutetium-PSMA-617 had a 38% improvement in OS, with a median OS of 15.3 months versus 11.3 months with standard of care. Their rPFS was improved by 60%, with a median of 8.7 months with ¹⁷⁷lutetium-PSMA-617 versus 3.4 months with standard of care. A secondary end point, time to first symptomatic skeletal event (SSE) was 11.5 months versus 6.8 months, respectively.

In terms of toxicity, there was an increase in high-grade adverse events for ¹⁷⁷lutetium-PSMA-617, including grade 3 and 4 hematologic toxicity in 10% of patients. Other AEs included gastrointestinal (GI) toxicity and dry mouth. Overall, Morris says this therapy offers favorable efficacy and acceptable toxicity in this patient population.

TRANSCRIPTION:

0:08 | VISION was a phase 3 randomized study which took patients whom I just described, that is those who had progressed through androgen receptor signaling inhibitor and who had progressed through chemotherapy. These patients were PSMA-avid on a gallium-68 PSMA 11 scan. The design of the trial was patients before randomization were given a protocol defined as standard of care by their treating physician and then randomized to either receive Pluvicto or not.

0:44 | Those who received Pluvicto had about 40% improvement in OS, about a 60% improvement in terms of rPFS, a 50% improvement in the likelihood of remaining free of a SSE. And in terms of toxicity, a modest amount of grade 3 and 4 hematologic toxicity, around 10%. [There was] some mild GI toxicity, around 40% of patients, [and] xerostomia in around 40% of the patients, also mild. So relatively, for this advanced patient population, a relatively favorable trade-off in terms of risk versus benefit in favor of treatment.