Pluvicto Improves rPFS in PSMA-Positive mCRPC

Shreeram Aradhye, MD

Treatment with lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617) led to a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) following treatment with an androgen receptor (AR) pathway inhibitor compared with a change in AR pathway inhibitor in patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), according to topline findings from the phase 3 PSMAfore trial (NCT04689828).¹

This represents the second positive phase 3 trial for lutetium Lu 177 vipivotide tetraxetan following the read out of the phase 3 VISION trial (NCT03511664), in which the radioligand therapy plus standard of care treatment led to a statistically significant reduction in the risk of death compared with SOC alone following treatment with an AR pathway inhibitor and taxane-based chemotherapy.

The phase 3 data will be presented at an upcoming medical meeting and discussed with the FDA in 2023 for regulatory approval.

“With the announcement of these positive topline phase 3 results, Pluvicto becomes the first PSMA-targeted radioligand therapy to demonstrate significant and clinically meaningful benefits for people living with this type of prostate cancer who have not received taxane-based chemotherapy,” Shreeram Aradhye, MD, president of Global Drug Development and chief medical officer at Novartis, said in a press release. “We look forward to discussing the data with healthcare authorities in order to bring this innovative new early treatment option to many more prostate cancer patients sooner after their diagnosis.”

On March 23, 2022, the FDA approved Pluvicto for the treatment of patients with PSMA-positive mCRPC who have previously received other anticancer therapies, such as AR pathway inhibition and taxane-based chemotherapy.²

PSMAfore is an open-label, multicenter phase 3 trial in which 469 patients with PSMA-positive, taxane-naïve mCRPC were randomly assigned 1:1 to treatment with lutetium Lu 177 vipivotide tetraxetan once every 6 weeks for 6 cycles, or a change in AR pathway inhibition.³ In both arms, patients were allowed to receive best supportive care including androgen deprivation therapy.

To be eligible for enrollment, patients must have progressed only once after receiving a second-generation AR pathway inhibitor, be 68Ga-PSMA-11 PET/CT scan positive, and have a castrate level of serum/plasma testosterone below 50 ng/dL or under 1.7 nmol/L.

The primary end point is rPFS, and evaluation of overall survival, which is a key secondary end point, is ongoing as data mature. Other secondary end points include time to second disease progression (PFS2), rPFS2, PFS, time to first symptomatic skeletal event, quality of life, and safety.

Notably, no unexpected safety findings occurred in the trial and were in line with the established safety profile of the agent.

References

1. Novartis Pluvicto™ shows statistically significant and clinically meaningful radiographic progression-free survival benefit in patients with PSMA–positive metastatic castration-resistant prostate cancer. News release. Novartis. December 5, 2022. Accessed December 5, 2022. https://bit.ly/3UywkJq
2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. FDA; March 23, 2022. Accessed December 5, 2022. https://bit.ly/3LaWA8w
3. 177Lu-PSMA-617 vs. androgen receptor-directed therapy in the treatment of progressive metastatic castrate resistant prostate cancer (PSMAfore). ClinicalTrials.gov. Updated November 8, 2022. Accessed December 5, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04689828