Lu-177-PSMA-617: another update

Because there is great interest in systemic therapies for metastatic prostate cancer, we want to provide readers with the latest news about the 177Lu PSMA-617 trials in Germany.

We recently reported (see this link) on 74 patients — 31% had PSA declines greater than 50% percent. A new report by Rahbar et al. expands the patient base to include PSA data on 99 patients and toxicity data on 121 patients treated at 12 therapy centers. After median follow-up of 16 weeks, and up to four therapy cycles:

  • 45 percent had a PSA decline greater than 50 percent.
    • 40 percent had a 50 percent decline in PSA after a single cycle.
  • 18/121 patients (15 percent) had serious or life-threatening hematotoxicity, affecting red blood cells (10 percent), platelets (4 percent), and white blood cells (3 percent).
  • Xerostomia (loss of saliva) occurred in 8 percent.

This is a very encouraging PSA response. For comparison, only 13 percent had a PSA reduction greater than 50 percent in the radium-223 diacetate (Xofigo) clinical trial. However in that trial, 66 percent had a 50+ percent decline in bone alkaline phosphatase, which may be a better biomarker for bone metastases. The hematotoxicity was identical.

Of course, what we really want to know is whether the treatment increases survival, and whether it is any better than Xofigo in doing so. The potential benefit of 177Lu PSMA-617 is that it can treat non-osseous metastases too. We await future clinical trials that may be able to prove such a benefit.

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



3 Responses

  1. Thanks for the update Allen. I would be interested in knowing if the patients who suffered severe marrow toxicity had also received chemotherapy. Do you have any details on this?

  2. John,

    I can’t say for sure, but I doubt that they would have received chemotherapy at the same time because both agents are known to be hematotoxic.

  3. I have been reading about lutetium treatment for some months, but I may still have much to learn. Lutetium-177 PSMA radioligand therapy come in at least three different forms: 177Lu J591, 177Lu-PSMA I&T, and 177Lu-PSMA-617. The first is a humanized monoclonal antibody. It has considerable myelosuppression. The two other drugs are small molecule enzyme inhibitors. Both have much less myelosuppression. The latter two are those most reported in the last year.

    Most studies have dealt with compassionate treatment of end stage patients multi-resistant to previous therapies. Therefore the response is surprisingly high because generally the effects of a drug goes down as a drug is shifted from first-line treatment to second-line treatment, third-line treatment, and so on.

    We have no information on how abiraterone, enzalutamide, radium-223, docetaxel, and carbazitaxel would have worked if these drugs had been used as something similar to compassionate treatment for (nearly) end-stage patients. But my guess is that the results would have been definitely poorer than the effects seen with these drugs as third-line therapy. And generally those results did not surpass those with lutetium-177 radioligand therapy.

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