Ac-225-PSMA-617 – A Treatment on the Horizon?

There are two phase 1 and 2 clinical trials reporting about a new PSMA targeting alpha emitting investigational radiation treatment.  The trials are evaluating Ac-225-PSMA-617.

 The first trial evaluated a cohort of men with end-stage (meaning they have failed many other treatments and had a life expectancy of 2 to 4 months) with advanced prostate cancer.

The trial report by Kratchowil et al. indicated that 40 men received three cycles of this treatment at the University of Heidelberg in two-month intervals.  They reported the following results:

1-     Eleven (11) men did not complete three cycles, - five (5) discontinued due to non-response; four (4) stopped due to xerostomia (dry mouth), and two (2) did not survive eight (8) weeks.

2-    There were thirty-eight (38) surviving men with 87% experiencing some PSA decline; 63% had a PSA decline greater than 50%; tumor control lasted a median of nine (9) months; five (5) men had a response lasting more than two (2) years.

 For comparison purposes prior therapies with abiraterone lasted ten (10.0) months, docetaxel lasted for six and one half (6.5) months, enzalutamide for six and one half (6.5) months, and cabazitaxel for six (6.0) months.

 Since the subject men were end-stage these outcomes are very impressive. 

 In the other early trial which was reported by Sathekge et al., seventeen (17) men who were chemotherapy-naive with metastatic prostate cancer were treated with Ac-225-PSMA-617 in South Africa. 

Most of the men had three (3) treatment cycles (every two months). Subsequent doses were lowered to control side effects. PSA and metastatic activity were tracked using Ga-68-PSMA-617 PET scans.  They found that:

1-    Sixteen (16) men responded to treatment

2-    In fourteen (14) men, PSA declined by over 90%

3-    In seven (7) men, PSA became undetectable after two (2) or three (3) treatments

4-    Fifteen (15) men had greater than 50% regression of their metastases

5-    Eleven (11) men had a complete resolution of their metastases

6-    Xerostomia (dry mouth) occurred in all of the subjects, but it was not severe (all Grade 1 or 2)

7-    Grade 3 anemia occurred in one (1) man who had extensive bone marrow metastases

8-    Grade 4 renal toxicity occurred in one (1) man with pre-existing Grade 3 renal failure

9-    Men reported a significant reduction in their bone pain

This study suggests that the investigational treatment Ac-225-PSMA-617 can be beneficial in men who have not been heavily pre-treated. It also demonstrates that the side effect, xerostomia (dry mouth) can be mitigated by reducing the subsequent doses and that for most patients, side effects are not severe enough to stop treatment. 

We have no way to compare this investigational treatment to the already approved beta radiation treatment Xofigo, or to the experimental therapy Lu-177 PSMA which is already in phase 3 clinical trials in the United States.   The possible advantage of the two PSMA treatments might be that Xofigo only targets cancer in bones, while the two PSMA treatments attack prostate cancer in both bone and soft tissue.

We now await the phase 3 clinical trials for Ac-225-PSMA-617.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs. He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.