Ac-225-PSMA-617 in mCRPC: an update


We now have some details from clinical trials of the radiopharmaceutical actinium-225-PSMA-617 (Ac-225-PSMA-617) in very advanced prostate cancer patients.

Kratchowil et al. have reported on 40 patients who received this treatment at the University of Heidelberg. All patients had progressed after multiple prior therapies and were expected to have a median projected survival of 2 to 4 months (see this link) at time of treatment. They received three cycles of Ac-225-PSMA-617 in 2-month intervals.

  • 11 patients did not complete the three cycles:
    • 5 discontinued due to non-response.
    • 4 discontinued due to xerostomia (dry mouth).
    • 2 did not survive 8 weeks.

However, among the 38 surviving patients:

  • 87 percent had some PSA decline.
  • 63 percent had a PSA decline of > 50 percent from baseline.
  • Tumor control lasted for an average (median) of 9.0 months.
  • 5/38 patients (13 percent) had a response lasting > 2 years.
  • The patients’ previous therapies with abiraterone had lasted for 10.0 months, with docetaxel for 6.5 months, with enzalutamide for 6.5 months, and with cabazitaxel for 6.0 months.

These outcomes are impressive for a therapy given when all other therapies have failed.

It is unclear whether Ac-225-PSMA is better than radium-223 acetate (Xofigo), the most effective of the radiopharmaceuticals approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). But Xofigo only attacks cancer in bones, whereas Ac-225-PSMA-617 attacks prostate cancer anywhere in the body. (Older radiopharmaceuticals like strontium-89 chloride/Metastron could only relieve pain and had no survival benefit.)

As of late 2016, the Heidelberg group had treated a total of 80 patients with this agent.

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

3 Responses

  1. The resuts are impressive. When comparing radium-223 treatment with actinium radio-ligand therapy (Ac-RLT), it is important to recall that radium-223 is only a treatment for bone metastases whereas Ac-RLT is a treatment of PSMA positive lesions whether they are bone metastases or visceral metastases.

    The important question is actually how Ac-RLT works relative to Lu-RLT. The two forms of RLT might differ in toxicity but less in efficacy.

    The authors should be complimented for the information given for duration of previous treatments with established life-prolonging drugs. For these drugs, efficacy goes down when the drugs is given later in the sequence of treatment, for instance comparing third-line treatment with second-line treatment. So the information of response duration adds to the thoughts of the proper place of RLT in the landscape of all available treatments for mCRPC.

  2. How does Ac-225-PSMA compare to lutetium-177 PSMA, Allen?

    One of our guys is about to start Lu-177 in LA this coming week.

  3. Rick,

    There’s never been a head-to-head comparison, as far as I know. These trials are small and the patient profiles can vary a lot from study to study. All I can tell you is that in the latest Lu-177-PSMA meta-analysis, Lu-177-PSMA elicited some PSA response in 68% and at least 50% PSA reduction in 37%, but that responses varied widely. The trade-off is that Lu-177 is a beta emitter with a longer range and less power, whereas Ac-225 is an alpha emitter with short range and more power.

    The other radiopharmaceutical of interest is I-131-MIP-1095 (currently in a dose-finding trial at MSKCC). It elicited some PSA response in 84% and at least 50% PSA reduction in 61%. I-131 is an even longer range beta emitter than Lu-177, and because it is strongly bonded to the ligand (not just chelated), it seems to have a higher effective dose.

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