Jorge A. Garcia, MD is the current director of the GU Medical Oncology clinical and research programs at University Hospitals Seidman Cancer Center.

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).

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.

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Jorge A. Garcia, MD, discusses the safety of Lu 177 vipivotide tetraxetan earlier in the treatment course for PSMA–positive mCRPC.

Garcia

[With this expanded approval], our patients can start using [lutetium Lu 177 vipivotide tetraxetan] even earlier. [It is] still restricted to a castration-resistance setting, but they now don't have to go through chemotherapy first to get it.”

Jorge A. Garcia, MD, chair of the Department of Solid Tumor Oncology at the Cleveland Clinic Taussig Cancer Institute, discussed the clinical impact of the FDA’s 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).

the FDA updated the indication for lutetium Lu 177 vipivotide tetraxetan

 to include adult patients with PSMA-positive mCRPC who have received prior androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy. The agent was 

initially approved by the regulatory agency

 in March 2022, but the original indication required patients with mCRPC to receive prior treatment with an ARPI and taxane-based chemotherapy.

The expanded indication allows use of lutetium Lu 177 vipivotide tetraxetan in a pre-chemotherapy setting and builds on the agent’s initial approval, which was based on findings from the phase 3 VISION trial (NCT03511664). With the new approval, patients may now receive the radioligand therapy following progression on an ARPI alone, provided they have PSMA-positive disease confirmed by PET imaging.

Garcia noted that this label revision addresses a clinical disconnect between molecular imaging findings and treatment access. He emphasized that PSMA expression is a functional biomarker, and patients with PSMA-positive scans should be eligible for PSMA-targeted therapies, regardless of prior chemotherapy exposure. The ability to initiate lutetium Lu 177 vipivotide tetraxetan earlier in the disease course reflects a biomarker-driven approach to treatment sequencing.

Previously, many patients eligible for lutetium Lu 177 vipivotide tetraxetan under the original label had heavily pretreated, late-stage disease, and they often exhibited cumulative toxicities and declining performance status, Garcia said. The revised indication now provides a therapeutic option for patients who have received androgen deprivation therapy and a next-generation ARPI but are not yet ready or eligible for chemotherapy.

Garcia explained that this change offers clinical benefit by preserving quality of life and deferring taxane-associated toxicities. It also reflects a broader shift toward the earlier integration of radioligand therapy in the treatment of mCRPC, he concluded.

Jorge A. Garcia, MD, discusses the clinical impact of the FDA’s expanded approval of lutetium Lu 177 vipivotide tetraxetan for PSMA-positive mCRPC.

Dr Garcia on the Effect of the Expanded Approval of Lutetium Lu 177 Vipivotide Tetraxetan in in PSMA+ mCRPC

Jorge A. Garcia, MD, Department of Hematology and Oncology, discusses the results of the randomized phase III METEOR trial, which compared the efficacy of cabozantinib (Cabometyx) versus everolimus (Afinitor) in patients with advanced renal cell carcinoma (RCC).

In the study, which led to the April 2016 FDA approval of cabozantinib for RCC, more than 600 patients were randomized to receive oral cabozantinb at 60 mg or everolimus at 10 mg daily. The primary endpoint was progression-free survival (PFS) with a secondary endpoint of overall survival (OS), Garcia explains.

Results showed that there was a significant PFS improvement in the patients who received cabozantinib versus everolimus, at 7.4 months and 3.9 months, respectively. The median OS was 21.4 months with cabozantinib and 16.5 months with everolimus. The objective response rate per independent review was 17% in the cabozantinib arm versus 3% in the everolimus arm. Subset analyses show that treatment with cabozantinib improves both PFS and OS, Garcia explains.

Jorge A. Garcia, MD, Department of Hematology and Oncology, discusses the results of the phase III METEOR trial, which compared the efficacy of cabozantinib (Cabometyx) versus everolimus (Afinitor) in patients with advanced renal cell carcinoma.

Dr. Jorge Garcia on METEOR Trial for RCC

Jorge A. Garcia, MD, Department of Hematology and Oncology, Cleveland Clinic, discusses some of the challenges with immunotherapy in prostate cancer.

The only immunotherapy agent approved to treat prostate cancer is sipuleucel-T. Moreover, Garcia explains practitioners caution use of sipuleucel-T because it is unclear if it is an active agent, and there are challenges with identifying patients who may benefit from it.

Other challenges with sipuleucel-T include lack of the following: PSA response, response evaluation criteria in solid tumors (RECIST), bone scan improvement, and symptom improvement. However, Garcia says patients are likely to have a better outcome with sipulencel-T than without it.

The next step in overcoming some of these challenges, Garcia predicts, is using sipuleucel-T in combination with oral therapies, such as enzalutamide or abiraterone acetate with prednisone. This could help mitigate side effects without decreasing the efficacy of sipuleucel-T.

Data suggest patients who may benefit from sipuleucel-T are those with low-volume or indolent disease; however, this subset may change if sipuleucel-T is used in combination with other agents. 

Jorge A. Garcia, MD

Articles

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

Dr Garcia on the Effect of the Expanded Approval of Lutetium Lu 177 Vipivotide Tetraxetan in in PSMA+ mCRPC

Dr. Jorge Garcia on METEOR Trial for RCC

Dr. Garcia on Challenges With Immunotherapy in Prostate Cancer