Dr Garcia on the Safety of Earlier Use of Lu 177 Vipivotide Tetraxetan PSMA+ mCRPC

"As we use these agents earlier, where [patients] are not as heavily pretreated, there may be a little bit of a difference in [adverse] effect profile compared with the post-chemotherapy space."

Jorge A. Garcia, MD, a genitourinary medical oncologist at University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, discussed the safety implications of administering lutetium Lu 177 vipivotide tetraxetan (Pluvicto) earlier in the treatment course for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC).

On March 22, 2024, the FDA expanded the indication for lutetium Lu 177 vipivotide tetraxetan to include adult patients with PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibitor (ARPI) and are considered appropriate to delay taxane-based chemotherapy. This regulatory decision was supported by findings from the phase 3 PSMAfore trial (NCT04689828), which demonstrated a radiographic progression-free survival (rPFS) benefit for lutetium Lu 177 vipivotide tetraxetan over a change in ARPI therapy in this patient population.

According to Garcia, the safety profile of lutetium Lu 177 vipivotide tetraxetan in this earlier, chemotherapy-naive setting remains favorable and consistent with prior experience in more heavily pretreated patients. The most commonly reported treatment-related adverse effects (AEs) include fatigue and anemia, occurring in approximately 20% to 25% of patients. Grade 3 or higher TRAEs were uncommon, with grade 3 or higher fatigue and anemia observed in approximately 5% of patients, and discontinuation due to toxicity remained low, he said.

The PSMAfore trial similarly reported that grade 3 or higher AEs occurred in 36% of patients receiving lutetium Lu 177 vipivotide tetraxetan vs 48% in those receiving an alternative ARPI. The rate of grade 5 AEs was 2% in both arms, with no grade 5 AEs attributed to the radioligand therapy.

Garcia noted that although earlier-line patients generally have more robust bone marrow reserve, routine hematologic monitoring remains essential due to the marrow-targeting nature of radioligand therapy. Additional observed toxicities include xerostomia, secondary to salivary gland uptake of the agent, although this effect was not dose-limiting in most cases.