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 …

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 …

Avoiding radiation damage to salivary glands with Ac-225-PSMA-617 therapy

As we await the results of the VISION trial of Lu-177-PSMA-617, research continues into improving radiopharmaceuticals. … READ MORE …

Onvansertib in treatment of abiraterone-resistant mCRPC

We hear that an investigational drug called onvansertib — a so-called polo-like kinase 1 (PLK1) inhibitor — may have benefit in the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) who are showing early signs of progression on treatment with abiraterone acetate (Zytiga) + prednisone.

… READ MORE …

Synergy between radiation of metastases and immunotherapy confirmed

Two clinical trials have now confirmed the abscopal or bystander effect in prostate cancer. These effects occur when cancer cells that are not directly treated are nonetheless killed. … READ MORE …

BET inhibition in treatment of mCRPC

A company called Zenith Epigenetics has recently reported data from a Phase I/II clinical trial of a drug known as ZEN003604 or ZEN-3694 in the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) who have progressed on treatment with either abiraterone + prednisone or enzlautamide (Xtandi). … READ MORE …

Ipatasertib meets one of two primary endpoints in Phase III trial

According to a media release issued by Roche earlier this morning, the company’s investigational drug known as ipatasertib met one but not both of the two primary endpoints in a randomized, double-blind Phase III trial known as the IPATential150 trial. … READ MORE …

Data from HERO trial reported — at virtual ASCO and in NEJM

The results of the Phase III HERO trial of relugolix — the first oral LHRH antagonist for treatment of advanced prostate cancer — have now been reported in the New England Journal of Medicine (NEJM) and at the “virtual” annual meeting of the American Society for Clinical Oncology (ASCO). … REAR MORE …

And now … FDA approves second PARP inhibitor for selected men with mCRPC

Following last week’s approval of rucaparib (Rubraca), the US Food and Drug Administration (FDA) has now, also, approved the PARP inhibitor olaparib (Lynparza) for the treatment of men with with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. … READ MORE …

FDA approves first PARP inhibitor for selected men with mCRPC

Yesterday evening the US Food and Drug Administration (FDA) approved rucaparib (Rubraca) for the treatment of men with BRCA1/2-mutant, metastatic, castration-resistant prostate cancer (mCRPC) who have also already been treated with androgen receptor-directed therapy and taxane-based chemotherapy. … READ MORE …

Sipuleucel-T in management of favorable-risk prostate cancer: the ProVent trial

At the end of last year, Dendreon announced that the Phase III ProVent trial of sipuelucel-T (Provenge) in the treatment of men with relatively lower-risk forms of prostate cancer (as compared to active surveillance) had been fully enrolled ahead of schedule. … READ MORE …

More negative data for checkpoint inhibition in treatment of mCRPC

Alas … once again we hear that the combination of  androgen receptor blockade (with enzalutamide/Xtandi) + a checkpoint inhibitor (the PD-L1 inhibitor atezolizumab/Tecentriq) has had no clinically meaningful impact on the overall survival (OS) of men with metastatic, castration-resistant prostate cancer (mCRPC) compared to enzalutamide alone. … READ MORE …

Olaparib in treatment of men with mCRPC and selected HRR gene mutations

According to a media release issued by AstraZeneca and Merck on Friday evening, olaparib (Lynparza) has shown “a statistically significant and clinically meaningful improvement in … overall survival (OS)” in men with metastatic, castration-resistant prostate cancer (mCRPC) and BRCA1/2 or ATM gene mutations (homologous repair gene mutations or HRRm). … READ MORE …