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 4-6 cycles)
After 24 weeks of follow-up after Cycle 2:
- 5 patients had PSA reduced by >50% (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
- 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.
