Ac-225-PSMA-617 apparently extends survival of very late-stage patients: an update


The nuclear medicine group at the University of Heidelberg in Germany recently reported a complete response in two patients treated with Ac-225-PSMA-617 (see this link).

A media release issued earlier this week by the Joint Research Centre of the European Commission now offers data on treatment of 80 patients using the radioactive alpha-particle emitter actinium-225 linked to a particular type of prostate-specific membrane antigen (PSMA) and at least 24 weeks of follow-up — with impressive results.

The 80 patients had all failed on multiple therapies and were only expected to have an average (median) survival of 2-4 months at time of study entry.

  • The response rate (PSA reduction and tumor shrinkage) was 75 percent.
  • Most patients were still alive 6 months after the therapy.
  • Dry mouth (xerostomia) was the only evident side effect of treatment.

We should be clear that this is a report from a media release, and not data published in a peer-reviewed journal. However, we will certainly report more details as they become available. We would also emphasize that truly dramatic results have been seen in just 2/80 patients so treated (2.5 percent).

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink. Also, given the relatively extraordinary outcomes from this type of unapproved, experimental therapy, we would note that patients interested in exploring the possibility of access to this therapy — which is still early in its development — can contact Dr. Uwe Haberkorn at the University of Heidelberg (by e-mail or by telephone at +49 6221 56-7731). We understand that Dr. Haberkorn speaks English.

6 Responses

  1. It would be really interesting if they can determine why those two patients did so well. Perhaps they have a genetic marker or a subtype of cancer that is susceptible to radiation. But then why did they not respond to Lu-177?

    It is intriguing to me that one of the two patients had liver mets and did well.

    It is always encouraging to hear when a therapy has such dramatic effects, if only in a small percentage of men. Hope is hopeful.

    Happy New Year

  2. Bill:

    I suppose that when the Sitemaster wrote “truly dramatic results were seen in just two patients” (that was his edit), he meant that a complete response was previously reported in 2 patients. But that doesn’t mean there weren’t excellent responses in many more patients. In fact, since the median survival was over 6 months, while expected survival was only 2-4 months, we know that many responses were excellent. We will have to see the peer-reviewed published results before we know the details.

    I don’t know why you say they did not respond to Lu-177-PSMA. We don’t know much about the natural history of PSMA, it seems to appear when prostate cancer cells reach a certain stage. Perhaps there is an optimum time when it is a useful target. About 5% of prostate cancers do not express it. Work continues on radiopharmaceuticals targeted to other cell proteins.

  3. Hi Allen.

    The article I read about the trial stated they had either failed or not responded to PSMA 617-Lu 177 prior to treatment with PSMA 617-Ac 225. I thought that was a fairly interesting point. I am not claiming to be an expert but since my disease is currently at the point of those men treated, I have a keen interest in the therapy and I am attempting to figure out if this is something I can or should pursue. A good friend and fellow warrior shared some of his research with me.

    In the article I read I did see the complete response of 2 patients but only one apparently had a durable response. I have seen other reports of complete response to the PSMA 617-Lu 177 therapy. In the past have spoken with my radiation oncologist about Lu-177 and have considered this therapy. At the time he advised me to wait; however, recently my disease has begun to progress significantly so I may not be able to wait too much longer.

    I am confident you are better informed on this subject and my response is only my musing as I work through my own personal process of deciding whether to pursue this for myself.

    Bill

  4. Hi.

    A correction to my earlier post: only Patient B had failed Lu-177 treatment. In Patient A it was contraindicated due to diffuse bone marrow involvement.

    My focus was on Patient B since he had liver involvement.

    Apologies

    Bill

  5. Bill:

    I didn’t know that they’d been pre-treated with Lu-177. Since the ligand is the same for both radiopharmaceuticals, the only difference is that Ac-225 (an alpha-emitter) is a much stronger cell killer than Lu-177 (a beta-emitter). Because Lu-177 has longer range, it may be possible to use both — the Lu-177 to kill larger metastases and the Ac-225 to kill micrometastases. Work continues to find more sensitive and selective ligands, and to find ligands that target different cancer cell proteins. Also, researchers are looking at attaching viruses and potentially toxic nanoparticles to those ligands.

    One concern I have is that much of the supply of Ac-225 is produced by separation from old nuclear reactor waste. This is tightly controlled, as you might imagine. The Idaho National Laboratory is producing supplies now, but it is part of the Dept. of Energy, which the incoming Secretary of Energy, Rick Perry, has threatened to close down. (Gov. Jerry Brown has vowed to keep the Lawrence Livermore and Berkeley Labs open, but I don’t know if there’s a savior for the Idaho Lab.) There are ways to produce it in a cyclotron, but they are more expensive and the isotopes they require are rare. So it’s anyone’s guess whether it will be possible in the future in the US.

  6. Allen:

    Thank you for the information about the isotope. Very interesting. I am going to do some research and speak with my doctors. If we all think it is appropriate treatment for me I would try to get treatment in Germany. I have no idea at this point if that is even a reasonable possibility.

    Bill

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