First clinical trial of Lu-177-PSMA-617 in recurrent, hormone-sensitive men

While we expect only a few months of extra survival from the VISION trial of Lu-177-PSMA-617 in heavily pretreated, metastatic, castration-resistant men (see this link), we hope to get more out of the radiopharmaceutical if used earlier.

Privé et al. reported the results of a pilot trial in 10 recurrent men treated with Lu-177-PSMA-617 at Radboud University in Nijmegen, The Netherlands. They were all:

  • Recurrent after prostatectomy ± salvage radiation (PSA > 0.2 ng/ml)
  • Rapid PSA doubling time (< 6 months)
  • Between 1-10 metastases detectable on a PSMA PET scan or USPIO MRI
  • At least 1 metastasis > 1 cm
  • Unable to receive SBRT to metastases
  • No visceral metastases
  • Have not begun salvage ADT
  • Treated with a low dose (3 GBq) on day 1; second treatment (~6 GBq) after 8 weeks (compared to dose in VISION trial of 7.4 GBq in each of 4 to 6 cycles)

After 24 weeks of follow-up after Cycle 2:

  • 5 patients had PSA reduced by > 50 percent (1 undetectable)
  • 2 patients had stable PSA
  • 3 patients had PSA progression
  • 6 patients had a radiographic response
  • 4 patients had radiographic progression
  • ADT-deferred survival was 9.5 months (median)
  • Those with lymph node only metastases had the best response
  • Those with any bone metastases had lesser response

After a second dose, comparing their 24-week PSA to their 12-week PSA:

  • PSA was continuing to decline in 3 patients
  • PSA was rising again in 6 patients
  • Side effects were mild (no grade 3) and transient:
    • Fatigue in 7;nausea in 3
    • Dry mouth (xerostomia) in 2

There are lots more questions than answers:

  • Would a higher dose and more treatments be more effective?
  • Would a higher dose and more treatments be more toxic?
  • Is it like Xofigo in that it’s more effective with micrometatases? If so, would a combination with SBRT targeted at the larger metastases be more effective?
  • Since it was more effective on lymph nodes, would it make a good combination with Xofigo for patients who have both lymph node and bone metastases? (See also Th-227-PSMA.)
  • Because there seems to be a continued abscopal effect for some patients, would combining it with Provenge be optimal?
  • Would pretreatment with ADT or a new anti-androgen (Xtandi, Erleada or Nubeqa) increase expression of PSMA, and increase radiosensitivity?
  • Can we predict who will benefit?

Use in other patient populations remains to be explored: high-risk, newly diagnosed metastatic, castration-resistant but chemo-naive. Optimal sequencing with other therapies remains to be explored.

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

New guidelines for management of advanced prostate cancer

The American Urological Association (AUA), together with the American Society for Radiation Oncology (ASTRO) and the Society for Urologic Oncology (SUO), has just issued a new set of guidelines for the management of advanced prostate cancer (see here). … READ MORE …

Areas of consensus at APCCC last year … see Table 1

So your sitemaster has been looking through the full report from the APCCC meeting held in Basel last year — as he promised he would. … READ MORE …

FDA approves enzalutamide for treatment of metastatic HSPC

Yesterday the U.S. Food and Drug Administration (FDA) approved the use of enzalutamide (Xtandi) for the treatment of metastatic, hormone-sensitive prostate cancer (mHSPC) — also known as metastatic, castration-rsensitive prostate cancer or mCSPC. … READ MORE …

Enzalutamide extends OS compared to an standard antiandrogen in ENZAMET trial, but …

The randomized, double-blind, Phase III ENZAMET trial was designed to investigate whether the combination of enzalutamide + standard androgen suppression had superior outcomes than a non-steroidal antiandrogen + standard androgen suppression in men with metastatic, hormone-sensitive prostate cancer (mHSPC). … READ MORE …

Full results of apalutamide in treatment of mHSPC

At the end of January, we had reported that the results of the TITAN trial — the Phase III trial of standard ADT + apalutamide (Erlead) or standard ADT + a placebo in men with metastatic, hormone-sensitive prostate cancer (mHSPC) — were positive, and that they were going to be reported at a meeting later in the year. … READ MORE …

ENZAMET trial results to be presented at ASCO

The results of the 1,125-patient, randomized, double-blind ENZAMET trial are to be reported in a late-breaking abstract at the upcoming annual meeting of the American Society for Clinical Oncology (ASCO) in Chicago. … READ MORE …

Long-term follow-up data from LATITUDE trial

Long-term follow-up data from the LATITUDE trial have now been published by Fizazi et al. in Lancet Oncology. … READ MORE …

Results from the ARCHES trial presented yesterday in San Francisco

On Thursday, here in San Francisco, Dr. Andrew Armstrong first presented the results of the so-called ARCHES trial of enzalutamide (Xtandi) + standard androgen deprivation therapy (ADT) in the treatment of men with metastatic, “hormone-sensitive” prostate cancer (mHSPC). … READ MORE …

Positive outcomes for apalutamide in the treatment of mHSPC

According to a media release issued late yesterday by Johnson & Johnson, the combination of apalutamide (Erleada) + androgen deprivation therapy (ADT) has met the primary study endpoints in the so-called TITAN trial. … READ MORE …

ODM-201 meets Phase III goal in treatment of nmCRPC

Like other, similar drugs before it, ODM-201 — now properly known by the generic name darolutamide — has apparently hit the primary goal of metastasis-free survival in the Phase III ARAMIS trial, as announced yesterday by Bayer and Orion. … READ MORE …

The potential for use of enzalutamide in HSPC: an update

We note that Pfizer and Astellas have recently modified the protocols for two large, international, randomized, Phase III clinical trials to see if they can get earlier results that might affect the potential for use of enzalutamide (Xtandi) in some groups of men with hormone-sensitive prostate cancer (HSPC). … READ MORE …

What’s the “best” form of first-line treatment for mHSPC today?

A new paper in the Annals of Oncology has addressed the critical question regarding what might be “the best” way we currently have to start treatment for a man newly diagnosed with metastatic, hormone-sensitive prostate cancer (mHSPC). … READ MORE …

ASCO issues new guidelines on treatment of metastatic prostate cancer

New guidelines on the management of metastatic, hormone-sensitive prostate cancer have just been released by the American Society for Clinical Oncology (ASCO), based primarily on data from the CHAARTED, STAMPEDE, and LATITUDE trial data. … READ MORE …

FDA approves abiraterone acetate for treatment of castration-sensitive, metastatic prostate cancer

Late yesterday the US Food and Drug Administration announced the approval of abiraterone acetate (Zytiga) + prednisone for the treatment of men with “high-risk, castration-sensitive”, metastatic prostate cancer. … READ MORE …