A review of the data from phase 3 randomized Phase 3 Study of 177Lu-PSMA-617 or best supportive/standard of care, VISION, in the treatment of patients with progressive PSMA-positive mCRPC and Dr. Morgans’ experience with 177Lu-PSMA-617.

Alicia Morgans, MD, MPH: The VISION trial was an international multi-institutional phase 3 trial that recently completed and demonstrated that treatment with 177Lu-PSMA-617 was associated with a prolonged radiographic progression-free survival and overall survival compared with best supportive care. This trial included patients with metastatic CRPC [castration-resistant prostate cancer] who had been exposed to treatment with an AR [androgen receptor]–directed therapy as well as docetaxel chemotherapy at a minimum. Patients may have had multiple therapies in addition to that.

Patients who were enrolled were randomized to best standard-of-care treatment, which could have been the alternate AR-targeted agent, pain medications, or even steroids vs that best standard of care plus 177Lutetium for 4 to 6 cycles. They were followed for radiographic progression-free survival [rPFS] and overall survival composite end point. We received a press release, a subsequent presentation, and a New England Journal of Medicine publication that explained that 177Lutetium plus best standard of care was associated with an improvement in rPFS and OS [overall survival] in this heavily pretreated population. Safety information from the New England Journal of Medicine publication and presentations demonstrated that 177Lutetium was generally well tolerated, and there were no new safety signals identified.

In this case, it was a wonderful idea to enroll the patient in the VISION clinical trial and give him the opportunity to undergo this treatment. I recall that it was very difficult to get a spot on that trial as patients were flocking to the centers because there had been such excitement regarding this therapy. To have the opportunity to go on the trial and then also receive 177Lutetium was great for this patient. If he had done standard of care, he could have considered things like cabazitaxel. He likely considered that, but he was probably deemed ineligible, which is why he became eligible to enroll in the VISION trial. The trial excluded patients who could receive cabazitaxel or radium as they could not be safely combined with 177Lu-PSMA-617 at the time. This option was great for this patient because presumably he didn’t have options like radium or cabazitaxel to use safely.

In my experience treating patients on the VISION trial, 177Lu-PSMA-617 was relatively easy to manage in terms of monitoring and safety. We kept an eye on patients’ bone marrow and watched for the development of cytopenias, because this is possible during treatment with 177Lutetium. We talked to our patients about xerostomia, or dry mouth, to ensure they were not developing severe dry mouth that could cause problems in terms of dental health or simply discomfort. In general, patients seemed slightly fatigued for a day or so after their treatment, but it was not extreme fatigue, and they felt there was minimal limitation. Otherwise, some patients were relatively symptomatic when they underwent treatment with 177Lutetium. Under my care and within a short period of time, some of their symptoms—including pain and fatigue—improved during treatment, and we were very happy to have the opportunity to enroll patients on the trial. Giving treatment with 177Lutetium was not more challenging than giving treatment with other radiopharmaceutical options like radium or chemotherapy, from my perspective.

In our experience with prostate cancer, we as a field have seen that most of our agents, when moved earlier in lines of therapy, are more effective. There’s a phase 3 clinical trial that’s being launched for men with metastatic hormone-sensitive disease looking at 177Lutetium in that patient population, and it will be interesting to see how patients tolerate the drug and how well it works in that setting. That’s still to be determined and why we’re doing the trial. There are other trials that are looking at 177Lutetium in even earlier patient populations to determine whether it can be helpful in an adjuvant or neoadjuvant setting and elsewhere. It’s important as a field that we give the opportunity of every drug that seems effective to be studied in different patient populations, so that we understand where it is most useful and how we can get the most out of it for the patients we see. Men come into our care at different states in their disease, and having many opportunities to use effective agents in those patients is always a good thing.

Transcript edited for clarity.

A 70-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer

May 2017

Initial presentation

A 70-year-old man presents with nocturia and decreased appetite

Clinical workup

  1. PMH: Unremarkable
  2. PE: DRE, enlarged prostate
  3. TRUS and biopsy revealed adenocarcinoma of the prostate gland, Gleason score 9 [5+4]
  4. CT showed minimal nodal involvement
  5. PSA 42 ng/mL, LDH 404 U/L
  6. His ECOG PS is 1


  1. Patient started on ADT with initial PSA response 12 ng/mL

December 2017

  1. Patient complained of right hip pain and abdomen pain
  2. Imaging with CT and bone scan showed 2 metastatic bone lesions in the pelvis and diffuse liver lesions
  3. PSA 30 ng/mL; Hb 9.4 g/dL; ANC 1.5
  4. Patient started on docetaxel, 6 cycles completed
  5. Follow-up imaging showed stable disease

November 2018

  1. PSA 40 ng/mL
  2. Routine imaging shows new metastatic bone lesions in the pelvis
  3. Patient started on abiraterone and prednisone, after 6 months he has a restaging scan which shows continued progression of disease

January 2019

  1. Patient had a 68Ga-PSMA-11 scan when screening for the VISION trial which shows several positive metastatic lesions in the pelvis and liver metastases
  2. He qualified on screening and enrolled in a clinical trial and treated with 177Lu-PSMA-617 as per the VISION protocol (7.4 Gbq [100 mCi] every 6 weeks for 4-6 cycles)
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