Dr Morris on the FDA's Expanded Approval of Lutetium Lu 177 Vipivotide Tetraxetan for PSMA+ mCRPC

“[The expanded indication] is a different clinical context in many respects. It [might] sound nominal to say [that] it's moved from a post-chemotherapy context to a pre-chemotherapy context, but that is quite a different patient population that's measured in years in terms of their potential for longevity."

Michael J. Morris, MD, a medical oncologist and head of the Prostate Cancer Section at Memorial Sloan Kettering Cancer Center, discussed the clinical significance of the FDA’s recent expanded approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) for the treatment of patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibitor therapy and are considered appropriate to delay taxane-based chemotherapy.

The expanded indication was supported by findings from the phase 3 PSMAfore trial (NCT04689828), which evaluated lutetium Lu 177 vipivotide tetraxetan vs a change in AR pathway inhibitor therapy in chemotherapy-naive patients with PSMA-positive mCRPC who experienced disease progression on a prior AR pathway inhibitor and were candidates to delay taxane-based chemotherapy.

Patients treated with lutetium Lu 177 vipivotide tetraxetan (n = 234) achieved a median radiographic progression-free survival (rPFS) of 9.3 months (95% CI, 7-not estimable) vs 5.6 months (95% CI, 4-6) for those who switched to a different AR pathway inhibitor (n = 234; HR 0.41; 95% CI, 0.29-0.56; P < .0001).

Previously, lutetium Lu 177 vipivotide tetraxetan was approved only for patients with PSMA-positive mCRPC who had progressed following AR pathway inhibitor therapy and taxane-based chemotherapy. This prior indication limited the agent’s use to patients with end-stage disease, many of whom were heavily pretreated and exhibited significant disease burden and organ dysfunction.

Morris explaind that with the recent expansion of the label, this radionucleotide may now be used in adult patients with PSMA-positive mCRPC who have progressed on AR pathway inhibitor therapy and are considered appropriate to delay chemotherapy.

Morris concluded that this shift in positioning—prior to chemotherapy—reflects a broader change in the management of mCRPC. Patients eligible for this approach will typically have received and progressed through androgen deprivation therapy and a next-generation AR pathway inhibitor.