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.

Lutetium-177 PSMA-617 in treatment of mCRPC: trial results

According to a media release, issued earlier today by Novartis, the company has provided preliminary data about the results of the international, multi-center, Phase III, randomized, VISION trial, which has been evaluating the efficacy and safety of lutetium-177 PSMA-617, a targeted radioligand therapy, in treatment of men with progressive, PSMA-positive, metastatic, castration-resistant prostate cancer (mCRPC) … READ MORE …

Active surveillance and related research: a new research initiative

As some of our readers will already be aware, Prostate Cancer International has been working in concert with Dr. M. Mihaj Siddiqui at the University of Maryland School of Medicine and the PATIENTS program at the University of Maryland School of Pharmacy to put together a grant request for funding for a program to identify evidence gaps to guide future research on the use of active surveillance to monitor low-risk prostate cancers. … READ MORE …

Modulating personal bias in provision of prostate cancer “support” services

As Howard Wolinsky has been learning over the past few years, not all prostate cancer support groups are “equal” — in the sense that individual support group leaders may be seriously biased by their own personal experiences (which may have occurred many years ago). … READ MORE …

Major new survey on active surveillance and prostate cancer

In February, a group of researchers initiated a major new survey of patient knowledge about active surveillance as an initial management option for men with lower risk forms of prostate cancer. … READ MORE …

Xofigo 2.0

Xofigo (radium Ra 223 dichloride) is a systemic radiopharmaceutical. Radium is chemically similar to calcium and is taken up by bones in places where bone is actively growing, as in prostate cancer bone metastases. … READ MORE …

Lu-177-PSMA-617 vs Jevtana (cabazitaxel): which should I do next?

We saw recently (see this link) that of chemotherapeutic and hormonal medicines for treatment of metastatic castration-resistant prostate cancer (mCRPC), Jevtana (cabazitaxel) is the preferred third-line treatment after Taxotere (docetaxel) and Zytiga (abiraterone acetate) or Xtandi (enzalutamide). … READ MORE …

AS and management of Grade Group 2 prostate cancer

The abstract of a presentation to be given by Egan et al. — from the National Institutes of Health (NIH) at Bethesda, MD — at the upcoming, virtual Genitourinary Cancers Symposium has indicated that active surveillance (AS) seems to be a very reasonable option for first-line management for compliant patients initially diagnosed with Grade Group 2 prostate cancer. … READ MORE …

ADT and risk for COVID-19 infection?

Early in 2020, in the initial stages of the COVID-19 pandemic, there was a suggestion (based on data from a small Italian study) that men who were using androgen deprivation therapy (ADT) to manage their prostate cancer might be at lower than average risk for becoming infected with this virus. … READ MORE …

“Dose painting”: simultaneous integrated boost to the dominant intraprostatic lesion

Two technologies have come together to allow for a new kind of radiation treatment known as simultaneous integrated boost (SIB), or, more informally, “dose painting.” … READ MORE …

SBRT for high-risk prostate cancer patients

As we have seen, stereotactic body radiation therapy (SBRT) is a preferred therapy for low- and intermediate-risk patients (see this link). It is effective, safe, convenient, and relatively inexpensive. However, its use for high-risk patients remains controversial. … READ MORE …

Mediterranean diet, active surveillance, and low-risk prostate cancer: the details

As we advised readers yesterday, a newly published study by Gregg et al. from the M. D. Anderson Cancer Center has given some clear indications that men diagnosed with lower-risk forms of prostate cancer who are initially managed on active surveillance (AS) can benefit — in terms of time to disease progression — from what is known as the Mediterranean-type diet. … READ MORE …

Mediterranean diet, active surveillance, and low-risk prostate cancer

The abstract of a newly published study on the use of the Mediterranean diet (MD) by men on active surveillance (AS) for management of low-risk, localized prostate cancer states that … READ MORE …

Whole pelvic salvage radiation may be better than precisely targeted lymph node salvage radiation

Last week, I looked at a retrospective study of metastasis-directed therapy (MDT) at the Mayo Clinic among oligorecurrent patients (see this link). … READ MORE …

FDA approves first, oral LHRH antagonist

Earlier today, the US Food and Drug Administration (FDA) approved relugolix, (Orgovyx, from Myovant Sciences), the first, oral luteinizing hormone releasing hormone (LHRH) receptor antagonist for the treatment of adult patients with advanced prostate cancer. … READ MORE …