Dr Morris on the FDA Approval of Lutetium Lu 177 Vipivotide Tetraxetan in PSMA+ mHSPC

“There are quite a few choices now, and it’s incumbent on all of us to generate the data as to who benefits most from which approach.”

Michael J. Morris, MD, the prostate cancer section head of genitourinary oncology and the Steven A. Greenberg Chair in Prostate Cancer Research at Memorial Sloan Kettering Cancer Center, discussed the significance of the July 2026 FDA approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic androgen pathway modulation–naive/sensitive prostate cancer, also known as metastatic hormone-sensitive prostate cancer (mHSPC).

For patients with BRCA2 mutations, the combination of abiraterone acetate and niraparib (Akeega) is already an FDA-approved treatment option, Morris began. Additional targeted therapies may soon expand the available armamentarium, he noted. Results from the phase 3 TALAPRO-3 trial (NCT04821622) have generated interest in the use of talazoparib (Talzenna)–based therapy for patients with alterations in DNA damage response genes involved in homologous recombination repair (HRR), although the exact scope of any future regulatory approval remains uncertain, he added. Whether the indication ultimately includes all HRR gene–positive tumors or is restricted to specific genetic alterations will help determine its clinical application.

Beyond HRR gene–directed therapy, treatment selection is increasingly influenced by other molecular biomarkers, Morris explained. Patients with PTEN-altered disease may be candidates for androgen deprivation therapy (ADT) combined with an ARPI and capivasertib (Truqap), he said. For patients with PSMA-avid disease, the combination of ADT, an ARPI, and lutetium Lu 177 vipivotide tetraxetan represents another promising strategy, he added. Meanwhile, patients who are not appropriate candidates for PSMA-targeted radioligand therapy or whose tumors lack sufficient PSMA expression may instead benefit from ADT, an ARPI, and docetaxel, he noted.

As the number of effective treatment options continues to grow, an important priority for future research will be identifying which patients derive the greatest benefit from each therapeutic approach, Morris said. Generating robust comparative data and refining biomarker-driven treatment selection will be essential to optimizing outcomes, he added.

The expanding role of PSMA-targeted therapies also highlights the importance of multidisciplinary care, Morris emphasized. Close collaboration among medical oncologists, nuclear medicine physicians, and radiation oncologists is increasingly necessary to coordinate treatment planning and ensure that patients receive the most appropriate, individualized care throughout the course of their disease, he concluded.