FDA Approves New Radioligand Therapy and Diagnostic for mCRPC

The US Food and Drug Administration (FDA) has approved a new radioligand treatment for certain men with metastatic castration-resistant prostate cancer (mCRPC), as well as a new radioligand diagnostic agent for use in imaging to identify men who are suitable for this treatment.

The new therapy is lutetium Lu 177 vipivotide tetraxetan (Pluvicto, from Advanced Accelerator Applications [Novartis]).

This product delivers high doses of beta radiation to prostate cancer cells by binding to prostate-specific membrane antigen (PSMA), which is highly expressed on the surface of prostate cancer cells but not on normal tissue.

The specific indication is for use in men with mCRPC who have already been treated with an androgen receptor pathway inhibitor and taxane-based chemotherapy and whose tumors express PSMA (which is seen in about 80% of men with prostate cancer, according to the manufacturer).

To find men with PSMA-positive mCPRP, the agency also approved a new diagnostic agent, gallium Ga 68 gozetotide (Locametz) for use with positron-emission tomography (PET).

These PET scans with Locametz can identify men who are suitable for treatment with Pluvicto.

The FDA noted that Locametz is the first radioactive diagnostic agent approved for patient selection in the use of a radioligand therapeutic agent.

Previously, the agency approved another version of a gallium diagnostic agent for PSMA-PET imaging in prostate cancer under an academic new drug application, but that approval covered use of the product for diagnostic purposes.

The manufacturer noted that Pluvicto is the first FDA-approved targeted radioligand therapy for eligible patients with mCRPC that combines a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle).

“The approval of Pluvicto is an important clinical advancement for people with progressing mCRPC, as it can significantly improve survival rates for those who have limited treatment options,” Oliver Sartor, MD, medical director at Tulane Cancer Center, commented in the company press release.

Clinical Data From VISION Trial

The new approval was based on clinical data from the VISION trial (NCT03511664), which show that use of Pluvicto significantly improved both overall survival (OS) and radiographic progression-free survival (rPFS), the FDA noted in its press release.

Median OS was 15.3 months in the Pluvicto arm, vs 11.3 months in the control arm; the hazard ratio for OS was 0.62 (95% CI: 0.52 – 0.74; P < .001).

Results from this trial were presented at the 2021 annual meeting of the American Society of Clinical Oncology, as reported at the time by Medscape Medical News.

At the meeting, trial investigators said the results show that adding Pluvicto to standard of care for patients who have already been treated with androgen receptor pathway inhibitors and chemotherapy significantly improves rPFS by 60% and OS by 38%.

“These findings warrant adoption of this product as a new treatment option in this patient population,” commented lead investigator Michael J. Morris, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City.

Experts not involved in the trial also welcomed the results, although one was critical of the trial design. In this VISION study, the comparator group received standard of care, which in this trial excluded chemotherapy, immunotherapy, radium-223, and investigational drugs. This means that Pluvicto was compared to “nothing,” inasmuch as the standard of care was “in essence” a placebo, noted Thomas Hope, MD, associate professor of radiology at the University of California, San Francisco.

Also, the patients in this study had prostate cancer that had progressed after chemotherapy and the use of androgen receptor pathway inhibitors, which is “a pretty narrow label” and “very end-stage,” he commented.

Another expert who was approached for comment, Jeremie Calais, MD, assistant professor of translational theranostics at the University of California, Los Angeles, was concerned about finding patients who could benefit from this new therapy.

He told Medscape Medical News that PET shows “where the PSMA target is expressed on the whole-body level,” and patients who respond well are those in whom all of the prostate cancer lesions have high PSMA expression.

“What really drives the prognostics,” he continued, “is the lesions with low PSMA lesions” or those that are negative for PSMA.

What that means in practice, Calais said at the time, is that “we should use PSMA PET to exclude patients that have PSMA-negative lesions or lesions with low PSMA expression, rather than including patients with sufficient PSMA positivity.”

Thus, PSMA PET scans should be a tool to “exclude rather than include” patients for this treatment, he added.

With that said, he believes that in pairing PSMA PET with an effective targeted treatment, the study is a “major milestone for the whole theranostics field…and it opens the door to many more trials to come in the PSMA domain,” as well as other areas.

The FDA has provided full prescribing information for Pluvicto and for Locametz.

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