The FDA has approved an expanded indication for Novartis’ radioligand therapy Pluvicto (lutetium Lu 177 vipivotide tetraxetan), allowing its use in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have received one androgen receptor pathway inhibitor (ARPI) but have not yet undergone chemotherapy.

The decision is based on data from the Phase III PSMAfore trial, in which Pluvicto demonstrated a 59% reduction in the risk of radiographic progression or death compared to a change in ARPI. Median radiographic progression-free survival more than doubled, increasing from 5.6 months in the control group to 11.6 months for patients receiving Pluvicto.

The Palo Alto, California-based company noted that this expanded indication nearly triples the number of patients eligible for the therapy.
“The earlier indication for Pluvicto could really change our treatment paradigms for patients with mCRPC,” said Dr. Michael Morris, prostate cancer section head at Memorial Sloan Kettering Cancer Center and principal investigator of the PSMAfore trial. “It offers a targeted therapy that better delays disease progression compared to a second ARPI.”

Although overall survival in the trial numerically favored Pluvicto, the difference was not statistically significant due to high crossover from the control group. Adjusted analyses using established statistical methods suggested a survival benefit.

Safety data from the trial indicated a manageable side effect profile, with the most common adverse events being dry mouth, fatigue, nausea, and constipation — mostly grade 1 or 2.

This update positions Pluvicto as the first and only PSMA-targeted radioligand therapy available before chemotherapy in this patient population. Novartis reports that its U.S. manufacturing infrastructure is fully equipped to meet demand, with capabilities to deliver the therapy to nearly 600 treatment sites nationwide.

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