THE "NEW" PROSTATE CANCER INFOLINK

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.

Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: hormone-sensitive, Lu-177 PSMA, metastatic hormone-sensitive prostate cancer |