FDA Expands Approval of Pluvicto in Combination with ARPI for PSMA-Positive mAPMN/S Prostate Cancer

The Food and Drug Administration (FDA) has issued an expanded approval of lutetium LU 177 vipivotide tetraxetan (Pluvicto, Novartis). Pluvicto may now be utilized in combination with an androgen receptor pathway inhibitor (ARPI) for the treatment of PSMA-positive metastatic androgen pathway modulation-naïve/sensitive (mAPMN/S) prostate cancer (PCa).

Novartis emphasized that Pluvicto may provide a viable option in this patient population as currently half of patients with mAPMN/S PCa (previously referred to as metastatic hormone-sensitive PCa) will progress to castration-resistant PCa within a 20-month period. The company also noted that approximately a third of patients with mAPMN/S PCa do not achieve undetectable prostate-specific antigen (PSA) levels with the ARPI/androgen deprivation therapy (ADT) combination.

"Pluvicto is now approved across PSMA-positive metastatic prostate cancer, nearly doubling the number of patients who may benefit from this targeted approach," noted Victor Bultó, the president of Novartis in the United States. "Patients with metastatic prostate cancer continue to face significant unmet need, underscoring the importance of introducing precision options earlier in the treatment journey.”

What the PSMAddition Trial Revealed About the Potential Of Pluvicto In Reducing Mortality Risk in Patients with Prostate Cancer

The expanded indication was based on findings from the phase III PSMAddition trial that were presented at the European Society for Medical Oncology (ESMO) conference in October 2025.

In comparison to the ARPI/ADT combination for patients with PSMA-positive mAPMN/S prostate cancer, researchers found that the combination of Pluvicto and ARPI led to a 28 percent reduction in the risk of radiographic progression or death.

Subsequent analysis of the PSMAddition trial found a 33 percent reduction in the risk of progression or death and trending data suggesting a 20 percent in overall survival, according to Novartis.

(Editor’s note: For additional content on prostate cancer imaging, click here.)

Scott T. Tagawa, M.D., the lead author of the PSMAddition trial, previously noted the favorable safety profile of the Pluvicto/ARPI combination in this patient population.

“These findings suggest that combining ¹⁷⁷Lu-PSMA-617 with standard of care hormonal therapy offers patients more time without disease progression, a safety profile with adverse events that are most often low grade and managed with supportive care, and an encouraging trend in overall survival,” said Dr. Tagawa, a professor of medicine at Weill Cornell Medicine and a medical oncologist at New York-Presbyterian/Weill Cornell Medical Center.

Could the Expanded Approval of Pluvicto Enhance Early Intervention for Patients with Prostate Cancer?

Michael Morris, MD, a principal investigator of the PSMAddition trial, said the expanded indication for Pluvicto represents a significant advance in facilitating earlier intervention for patients with PSMA-positive mAPMN/S PCa.

“The treatment landscape for mHSPC is evolving, and this approval reflects a growing recognition that earlier treatment intensification matters. Having a radioligand therapy available at this stage meaningfully expands the options for physicians and represents real progress for patients,” emphasized Dr. Morris, the prostate cancer section head of genitourinary oncology at Memorial Sloan Kettering Cancer Center in New York City.