Showing posts with label Lu-177. Show all posts
Showing posts with label Lu-177. Show all posts

Saturday, April 13, 2024

Pluvicto+Xtandi Delays Progression Better than Xtandi-alone in mCRPC

Both Pluvicto (177LuPSMA-617) and Xtandi (enzalutamide) have been separately shown to delay progression and extend survival among metastatic and castration-resistant men with prostate cancer (mCRPC). Because they inhibit prostate cancer in different ways, it was hoped that combining them would have an additive benefit. In a clinical trial, enzalutamide temporarily increased expression of PSMA, so a synergistic effect is possible.

Emmett et al. reported the first results of the ENZA-p trial. 162 mCRPC patients with 2 or more risk factors were treated at 15 hospitals in Australia. Unlike the VISION trial, they did not previously receive docetaxel or 2nd line hormonal treatment for mCRPC. The risk factors were:

  1. metastatic at original diagnosis
  2. elevated LDH, ALP, albumin (PSA> 5 ng/ml)
  3. PSADT< 84 days
  4. < 3 years since diagnosis
  5. ≥5 bone or visceral metastases 
  6. pain requiring opiates
  7. received abiraterone for mHSPC (docetaxel for mHSPC was allowed)

After 20 months of follow-up, the outcomes were:

  • Median PSA Progression-Free Survival was 13.0 months for the combo vs 7.8 months for enza-only
  • Median Radiographic Progression-Free Survival was 16 months for the combo vs 12 months for enza-only
  • Percent with >50% PSA reduction was 93% for the combo vs 68% for enza-only
  • Percent with >90% PSA reduction was 78% for the combo vs 37% for enza-only
  • Too early for overall survival
  • Improvement in pain scores were 61% for the combo vs 27% for enza-only
  • Side effects for the combo vs enza-only were fatigue (75% vs 70%), nausea (47% vs 27%), and dry mouth (40% vs 10%).
  • 81% received all 4 doses of Pluvicto.

Based on these results, and pending later follow-up on overall survival, Pluvicto should be combined with enza.



Friday, April 30, 2021

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 4-6 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
After 2nd 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.






Tuesday, August 11, 2020

PSMA-targeted radiopharmaceutical clinical trials in the US

(frequently updated)

Now that the VISION trial of Lu-177-PSMA-617 is no longer recruiting, some patients are wondering if they can still get PSMA-targeted radiopharmaceuticals in the US, without traveling to Germany, Australia, India, etc. Here is a list of trials that are active, still open to recruitment, or will soon be recruiting. 

Unless otherwise noted, they are all for men who are: 

  • metastatic
  • castration-resistant 
  • have had at least one taxane chemotherapy
  • at least one of the advanced androgen receptor therapies (e.g., Zytiga, Xtandi, Erleada, or Nubeqa)
  • no Xofigo
  • PSMA-avid on a PSMA PET/CT scan

Radiopharmaceutical

Adjuvant drugs

Extra criteria

Recruitment status/ contact

Locations

Lu-177-PSMA-617 

LuCarbo

Carboplatin


Not yet recruiting

Dana-Farber, Boston


Lu-rhPSMA-10.1


•Recurrent postRP

•regionally positive on PSMA PET

recruiting

Emory,  Atlanta

Lu-177-JH20002


•Advanced PCa

recruiting

•California

•Florida

•Michigan

Lu-177-PSMA-617

PSMACare

1. ADT

2.ARSi+ADT (ARSi=Zytiga, Xtandi,Erleada or Nubeqa)

•Metastatic with PSMA PET, but not with conventional imaging

•CRPC

•No prior ARSi or chemo

recruiting

TBD

Lu-177-PNT2002

LUNAR

Before SBRT

Recurrent and oligometastatic

recruiting

UCLA

Ac-225-J591

ACTION

SBRT,

ADT if polymetastatic

Recurrent

# mets 

recruiting

Weill Cornell

Lu-177-rhPSMA-10.1


±previous chemo

recruiting 

•Maryland

•St.Louis

•Omaha

•Mt Sinai-NYC

Lu-177-PSMA-I&T


Chemo naïve, failed one hormonal

recruiting

• 56 locations

Ac-225-PSMA-I&T

TATCIST



Recruiting

• Houston

Ac-225-J591

 

 

recruiting

• Weill Cornell

• Brooklyn Methodist

Pluvicto+ONC392 (a CTL4 blocking immunotherapy)



recruiting

• NYU Langone

• Columbia


Ac-225-J591 + Lu-177-PSMA- I&T

 

 

recruiting

• Weill Cornell

• Brooklyn Methodist

Ac-225-J591

Keytruda

No chemo since castration resistant

recruiting

• Weill Cornell

• Brooklyn Methodist

• Dana Farber

• Columbia

Cu-67-SAR-bisPSMA

SECuRE

 

Previous chemo OK, not required

recruiting

• Johns Hopkins

•Mayo Rochester

•Mayo, AZ

•Tulane, N.O.

•Barnes Jewish, St. Louis

•Omaha, NE

•Weill Cornell

Lu-177-PSMA-617

PSMAddition


mHSPC

(M1 or N1)

Treatment naive

Recruiting

• 174  sites

Lu-177-PSMA-617

Keytruda

No chemo since castration resistant

active, not recruiting

UCSF

Lu-177-CTT1403

 

No Jevtana

active, not recruiting

UCSF

Lu-177-PSMA-617

 

 

Active, not recruiting

•Weill Cornell

•Tulane

Th-227-Antibody

(see article)

 

 

active, not recruiting

• Royal Marsden (UK)

• Finland

• Tulane

• MSK

• Omaha, NE

Lu-177-J591

Ketoconazole

Prior RP or RT

CRPC

Non-metastatic

active, not recruiting

• Weill Cornell

• USC

• Georgetown

• IU

• U of Iowa

• UPMC

Lu-177-PSMA-R2

 

 

Active, not recruiting

• Stanford

• Yale

• Tulane

• Johns Hopkins

• Mt Sinai

• MD Anderson

• U of Wisconsin

• Phoenix

Lu-177-PSMA-617

PSMAfore

 

Chemo and immunotherapy naïve, failed one hormonal

Active, not recruiting

(Phase 3 RCT)

• 72  sites

Lu-177-PSMA-617

(VISION)

 

 

Active, not recruiting

• 84 locations

Results expected August 2020

I-131-1095-MIPS

(see article)

Xtandi

Chemo naïve

Failed Zytiga

Active, not recruiting

• 17 locations

Results expected December 2021