Friday, August 26, 2016

Lu-177-PSMA Update


One of the more important emerging radiotherapies for metastatic castrate-resistant prostate cancer is Lu-177 that is chemically bonded to a ligand -- an antibody or a small molecule that attaches to the prostate-specific membrane antigen (PSMA). We’ll call this class of medications Lu-177-PSMA. PSMA is expressed on the surface of 95% of all metastatic prostate cancer cells. See this link for a fuller explanation. Many of the studies on Lu-177-PSMA have been conducted in Germany. Recently, there was a report on a small study from Bad Berka, Germany with some early encouraging results. There have been a few more trial reports since then.

All of the more recently published studies used a ligand called PSMA-617, a small molecule that attaches to PSMA, rather than a PSMA antibody. It was hoped that this ligand would be more specific to prostate cancer cells, with less affinity for salivary glands and kidneys where it can cause side effects and false positives.

Kratchowil et al. at the University of Heidelberg reported on 30 patients treated with one to three cycles of Lu-177-PSMA-617.
  • ·      PSA decreased in 21/30 patients (70 percent).
o   PSA decreased by > 50% in 13/30 (43 percent)
o   Among 11 patients who had 3 cycles of therapy, 8 (73%) had PSA declines >50% that were sustained for over 24 weeks. Number and size of metastases decreased as well.
  • ·      Hematotoxicity (from bone marrow suppression) was mild.
  • ·      Xerostomia (dry mouth), nausea and fatigue were transient and occurred in <10 percent.
  • ·      Excess radioactivity was cleared from the kidneys within 48 hours.
Rahbar et al. at the University Hospital M√ľnster reported on 74 patients treated with a single dose of Lu-177-PSMA-617.
  • ·      PSA decreased in 47/74 patients (64 percent).
o   PSA decreased by > 50% in 23/74 patients (31%)
  • ·      PSA was stable (- 50% to +25%) in 35/74 patients (47%)
  • ·      PSA increased by > 25% in 17/74 patients (23%)
  • ·      No significant loss of red blood cells, white blood cells or kidney function
  • ·      Mild decline in platelets, but within normal range

Rahbar et al. also report outcomes on 28 patients after one vs. two treatments.
  • ·      PSA decreased in 59% of patients after 1 treatment and in 75 percent after 2 treatments.
o   PSA decreased by > 50% in 32 percent of patients after 1 treatment and in 50% after 2 treatments.
  • ·      Median survival was 29 weeks, compared to 20 weeks based on historical expectations.
  • ·      No clinically significant or lasting toxicity occurred.

Radiotherapy with Lu-177, though encouraging, is still in its early days. There is much work to be done in identifying the optimal ligand, optimal dose, optimal number of treatments, optimal patient/disease characteristics, and adjuvant therapies. I encourage participation in clinical trials in the US (NCT00859781) and in Germany.



2 comments:

  1. Alan, nice site with much good information. The group at Cornell under Scott Tagawa is also doing 177Lu-PSMA-617 therapy. This approach is called theranostics (i.e., imaging and treatment).

    DKFZ-PSMA-617 has been also used as a theranostic agent with 68Ga-DKFZ-PSMA-617 for imaging & 177Lu-DKFZ-PSMA-617 for endoradiotherapy. The major work done on this compound was by Benesova et al.

    ReplyDelete
    Replies
    1. Thanks. Scott Tagawa's studies and clinical trials were discussed in an earlier article titled "Will Lu-177-anti-PSMA be the next Xofigo?" https://pcnrv.blogspot.com/2016/08/will-lu-177-anti-psma-be-next-xofigo.html . He has started a dose-finding trial for men with mCRPC. Another trial has begun with sites in Houston and expected at UCLA: https://clinicaltrials.gov/ct2/show/NCT03042312 . However, it is very expensive and not covered by insurance. Interested patients may find that medical tourism to Germany may be less costly, and the doctors are certainly more experienced. Coincidentally, I just published an article about a new ligand today. At the end is a list of previously published articles on the subject: https://pcnrv.blogspot.com/2017/09/a-new-lu-177-psma-ligand-has-good.html

      Delete