Targeted Radioligand Therapy Shows Efficacy in PSMA-Positive mCRPC

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.