The US Food and Drug Administration has approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in combination with an androgen receptor pathway inhibitor for adults with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naive or -sensitive prostate cancer, according to a press release from Novartis. The company stated that the expanded indication nearly doubles the number of patients eligible for treatment.

The approval was based on the phase 3 PSMAddition trial, which compared Pluvicto plus standard of care, consisting of androgen deprivation therapy and an androgen receptor pathway inhibitor, with standard of care alone. Pluvicto plus standard of care reduced the risk of disease progression or death by 28% compared with standard of care alone. In an updated analysis, the combination reduced the risk of disease progression or death by 33% compared with standard of care alone. The updated analysis also reported a positive trend in overall survival favoring the Pluvicto combination, although the overall survival data continue to mature pending the final analysis.

According to Novartis, more than 186,000 men are diagnosed with metastatic hormone-sensitive prostate cancer each year globally. The press release stated that approximately one-third of patients do not achieve undetectable prostate-specific antigen levels with androgen receptor pathway inhibitor plus androgen deprivation therapy alone and that about half will progress to castration-resistant disease within 20 months. Prostate-specific membrane antigen is expressed in tumors from more than 80% of patients with prostate cancer, according to the company.

The safety and tolerability profile of Pluvicto was reported to be consistent with that observed in the PSMAfore and VISION studies. At the primary analysis, grade 3 or higher adverse events were reported in 51% of patients receiving Pluvicto plus standard of care and 43% of those receiving standard of care alone. The most common all-grade adverse events were dry mouth, fatigue, nausea, hot flush, and anemia. According to the company, health-related quality-of-life remained stable over time, with similar outcomes in both treatment groups.

Pluvicto is an intravenous radioligand therapy composed of a targeting compound linked to the therapeutic radionuclide lutetium-177. Following intravenous administration, Pluvicto binds to target cells, including prostate cancer cells that express PSMA. According to Novartis, emissions from lutetium-177 damage the target cells and nearby cells, disrupting cell replication or inducing cell death.

Source: Novartis