FDA expands Pluvicto approval to earlier-stage metastatic prostate cancer, nearly doubling eligible patients
The U.S. Food and Drug Administration on July 31, 2026, approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) in combination with an androgen receptor pathway inhibitor for patients with PSMA-positive metastatic hormone-sensitive prostate cancer. The expanded approval allows treatment of earlier-stage metastatic disease, nearly doubling the eligible patient population, Novartis officials said.
The expanded FDA approval allows Pluvicto to be used in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC) who have not yet undergone androgen receptor pathway inhibition or chemotherapy, according to Novartis officials. This approval covers metastatic castration-sensitive prostate cancer (mCSPC) and metastatic androgen pathway modulation–naive/sensitive (mAPMN/S) disease, broadening the therapy’s use beyond its prior authorization for metastatic castration-resistant prostate cancer (mCRPC). Novartis representatives said the new indication nearly doubles the number of patients eligible for Pluvicto in the United States, reflecting the larger population of hormone-sensitive metastatic patients compared with those in later-stage castration-resistant disease.
Pluvicto reduced the risk of disease progression or death by 28% in the primary analysis (hazard ratio [HR] 0.72; 95% confidence interval [CI], 0.58–0.90).
The FDA’s decision on July 31, 2026, was based on results from the Phase III PSMAddition trial, which evaluated Pluvicto combined with standard of care—an androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT)—against standard of care alone. According to trial data presented by Novartis, An updated analysis showed an even greater risk reduction of 33% (HR 0.67; 95% CI, 0.55–0.82). Overall survival data indicated a positive trend favoring Pluvicto plus standard of care (HR 0.80; 95% CI, 0.63–1.01), though the final overall survival analysis is pending, Novartis officials said.
Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, is a targeted radioligand therapy that delivers beta-emitting lutetium-177 directly to prostate-specific membrane antigen (PSMA)–expressing prostate cancer cells. The therapy requires confirmation of PSMA-positive disease via FDA-approved PSMA PET imaging agents, such as Locametz (gallium Ga 68 gozetotide), consistent with prior labeling requirements. The recommended dosing for the mCRPC indication is 7.4 gigabecquerels (200 millicuries) administered intravenously every six weeks for six doses or until disease progression or unacceptable toxicity, according to FDA prescribing information.
Pluvicto was first approved by the FDA on March 23, 2022, for adults with PSMA-positive metastatic castration-resistant prostate cancer who had previously received both androgen receptor pathway inhibition and taxane-based chemotherapy. That approval was supported by the Phase III VISION trial, which demonstrated significant improvements in overall survival and radiographic progression-free survival. In VISION, Pluvicto plus best standard of care yielded a median overall survival of 15.3 months compared with 11.3 months in the control arm (HR 0.62; 95% CI, 0.52–0.74). Approximately 30% of patients treated with Pluvicto showed an overall response by RECIST 1.1 criteria, compared with 2% in the control group, records show.
On March 28, 2025, the FDA expanded Pluvicto’s indication to include adults with PSMA-positive mCRPC who had received ARPI therapy and were appropriate to delay taxane-based chemotherapy. This earlier use was supported by the Phase III PSMAfore trial, which showed that Pluvicto reduced the risk of radiographic progression or death by 59% compared with switching ARPI therapy (HR 0.41; 95% CI, 0.29–0.56; p<0.0001). Updated analyses from PSMAfore indicated that Pluvicto more than doubled median radiographic progression-free survival to 11.6 months compared with 5.6 months for ARPI change, according to trial investigators.
The 2026 approval for hormone-sensitive metastatic disease builds on these prior expansions by moving Pluvicto earlier in the metastatic prostate cancer continuum. Novartis officials described this as advancing a potential new standard of care across PSMA-positive metastatic prostate cancer. Industry sources and academic reviewers have noted that the shift allows for radioligand therapy to be integrated before chemotherapy in mCRPC and now in hormone-sensitive metastatic settings, potentially altering treatment sequences.
Patient selection for Pluvicto requires PSMA-positive metastatic disease confirmed by approved imaging. For the expanded mCRPC indication, patients must have prior ARPI exposure and be clinically appropriate to delay taxane chemotherapy. The therapy’s targeted mechanism offers precise tumor delivery with reduced systemic toxicity compared with conventional systemic treatments, according to peer-reviewed analyses cited by Novartis and academic experts.
The Prostate Cancer Foundation has highlighted the significance of earlier Pluvicto use, noting that about half of mCRPC patients do not survive long enough to receive second-line therapies, underscoring the need for effective treatments earlier in the disease course. The foundation described the 2025 expanded approval as allowing use before chemotherapy to slow disease progression and maintain quality of life.
FDA communications and Novartis statements confirm that Pluvicto’s expanded indication now covers adults with PSMA-positive metastatic prostate cancer across both hormone-sensitive and castration-resistant stages. The therapy’s availability throughout the metastatic disease spectrum marks a shift from end-stage treatment to earlier intervention. The final overall survival data from the PSMAddition trial are anticipated to provide further clarity on long-term benefits in the hormone-sensitive setting.
