Ac-225-PSMA-617: another update


One of the more exciting new developments in radiopharmaceuticals for metastatic prostate cancer has been the development of alpha-particle emitters attached to PSMA ligands. We previously reported this update.

Sathekge et al. have now reported the outcomes of 17 chemotherapy-naive, metastatic castration-resistant patients treated with Ac-225-PSMA-617 in South Africa. Most patients had three treatment cycles (every 2 months). Subsequent doses were lower to prevent side effects. PSA and metastatic activity was tracked using Ga-68-PSMA-617 PET scans.

  • 16/17 patients responded to treatment.
  • In 14/17 patients, PSA declined by > 90 percent.
  • In 7 patients, PSA became undetectable after 2 or 3 treatments.
  • 15/17 patients had > 50 percent regression of metastases.
  • In 11 patients, there was complete resolution of metastases.
  • Xerostomia (dry mouth) occurred in all patients, but it was not severe (all Grade 1 or 2).
  • Grade 3 anemia occurred in 1 patient with extensive bone marrow metastases.
  • Grade 4 renal toxicity occurred in 1 patient with pre-existing Grade 3 renal failure.
  • Significant reduction in bone pain was reported

This study suggests that Ac-225-PSMA-617 is particularly beneficial in patients who have not been heavily pre-treated. It also shows that xerostomia can be mitigated by reducing the subsequent doses given, and that, for most patients, side effects are not severe enough to stop treatment. Lu-177-PSMA is now in a Phase 3 clinical trial at multiple sites in the US.

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

6 Responses

  1. Hi Mike.

    That certainly is an exciting development. Added to the research results reported earlier by the team in Australia, it certainly seems like “weaponizing” the PSMA scan may be a valuable treatment option for many of us who are looking for alternatives to chemotherapy.

    You mention a cautionary note about results for men who have been ” heavily treated”. Can you expand on that?

    I look forward to seeing you again at the upcoming conference in Virginia Beach on October 13th.

  2. Hi Al.

    Allen Edel wrote this commentary for us, so I’m going to need to let him respond.

  3. Hi Al,

    I am unaware of any trial results of Ac-225-PSMA from Australia, but would love to hear about it — could you please provide a reference? I am aware of a dose-finding trial by Scott Tagawa at Weill Cornell in NYC.

    Apparently in South Africa, there is unfortunately little use abiraterone, enzalutamide, and docetaxel, and patients present with progressed disease. So the patients were not pre-treated with any of those medicines. In fact, 4 of the 17 men had no previous treatment at all. Most (12) had prior ADT, and three had prior Lu-177-PSMA-617. I think they had the kind of PSA and radiographic response they would have had with first-line abiraterone or docetaxel.

  4. I want to add a recent anecdotal experience. Our dear AnCan Co-founder, Rob Barniskis, who passed late August, was in the midst of Lu-177 PSMA-617 treatment in Houston.

    After never exhibiting high PSAs for over 8 years, his numbers rocketed as the disease moved from soft tissue to bone. He started Lu-177 with a PSA a little over 1,000 and rising. It peaked at 1,700 a couple of weeks after his first treatment, then dropped precipitously to 250. Unfortunately Rob’s body was shot, and he was never strong enough to handle a second treatment.

  5. I think it need a clarification. The Vision trial in the US uses Lu-177 PSMA-617. Actinium-225 is not the same as Lu-177. It is a different particle emitter, and traditionally most concern has been severe xerotomy (total sicca syndrome) when Ac-225 PSMA has been given in cycles at a dose of 8 MB.

    I believe the reference to the Australian study is to a Lancet Oncology publication from Melbourne by Prof. Michael Hofman on 30 patients given Lu-177 PSMA. That was not a trial on Ac-225 PSMA.

  6. Dear Finn:

    It is perfectly clear to me that people are talking about two different things here. I think all that anyone is saying is that use of differing forms of Lu-177 PSMA and Ac-225 PSMA in the treatment of carefully selected patients with advanced prostate cancer at differing and appropriate doses is showing promise.

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