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European Society for Medical Oncology Congress - ESMO 2023 - Two Significant Lutetium Trials -mCRPC

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Those following information coming from the ESMO Congress over the last few weeks will be aware of the many presentations focussed on the use of Lutetium.

PSMAfore Study Unveils Game-Changing Results for Prostate Cancer Treatment

One such highlight was the results from the PSMAfore study – a phase three trial exploring PSMA -617 lutetium for taxane-naïve patients with metastatic castrate-resistant prostate cancer. Results of this study are discussed in the special UroToday presentation with Oliver Sartor.

Notable findings revealed significantly improved radiographic progression free survival with PSMA-617 lutetium vs a change in androgen receptor pathway inhibitors – some 12.02 months v 5.59 months in the control group plus extended time to symptomatic skeletal events, enhanced QOL and fewer adverse events in the lutetium arm.

Dr Sartor also noted the substantial crossover to lutetium when progression occurred in the control arm and acknowledged, although the overall survival data is immature, there is some indication that for this group there is a survival benefit with lutetium, meaning that even if there are delays in transitioning to lutetium there may still be benefits.

urotoday.com/trials-in-prog...

Enzalutamide and 177Lu-PSMA-617 in Poor Risk Metastatic Castrate Resistant Prostate Cancer (mCRPC) – ENZA-p study

The presentation of the results of this trial by Dr Louse Emmett, director of theranostics and nuclear medicine at St Vincent’s Hospital in Sydney, will be of interest generally to those who ‘sit’ in this high-risk group. It will also be special interest to those of us in Australia where Lutetium is not funded either by Medicare or private insurance regardless of whether you are castrate sensitive or resistant. An issue Dr Emmett is trying hard to rectify.

This phase 2 randomised trial of Enzalutamide and Lu-PSMA-617, in poor risk mCRPC evaluated the activity and safety of combining enzalutamide with adaptive dosing of LuPSMA vs enzalutamide alone as first line treatment for mCRPC. Participants had not previously been treated with chemotherapy or androgen receptor pathway inhibitors although prior treatment with abiraterone and/or docetaxel for hormone sensitive disease were allowed.

During the presentation Dr Emmett commented “This is the first randomized trial combining an androgen receptor signalling inhibitor, enzalutamide, with Lu-PSMA-617. It provides strong evidence for an enhanced anti-cancer effect with the combination of enzalutamide and Lu-PSMA-617 based on the primary end point, PSA-PFS”. Data from the study showed a median PSA-PSF of 13 months with the combination therapy compared with 7.8 months with enzalutamide alone. Median radiographic PFS was 16 months with the combination therapy compared with 12 months for enzalutamide. Additionally, decreases in PSA >50% response rates were 93% in the combination arm compared with 68% for enzalutamide alone.

Dr Emmett noted “We used 2 to 4 doses of Lu-PSMA in the ENZA-p trial, but 2 to 6 doses may further improve progression free survival, particularly in those patients who have a high proportion of androgen persistent clones.”

If this trial is of particular interest to you, a podcast interview with Dr Emmett by Dr Declan Murphy is expected in the next week.

urotoday.com/conference-hig...

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marnieg46
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NPfisherman profile image
NPfisherman

Marnie,

Thanks for posting this information from the conference. Lutetium is still in the early phase of being studied...Look for more compounds to be developed like Lu-177J-591 that can attach themselves to cancer based on targeting cancer antigens. The fact that they are testing on chemo naive patients is because chemo seems to decrease responsiveness to some therapies, especially immune related responses...

It is why I believe that chemo will eventually be moved to a position later in the treatment protocols. Checkmate 650 patients that were chemo naive had better responsiveness to the drugs (25%) vs those having prior chemo (10%).

I may throw Lu177 J-591 into the treatment plan for next time.... APCEDEN is also under consideration.

Keep things running smoothly at Peter Mac...

Dave

MateoBeach profile image
MateoBeach

Thanks Marnie for posting these. Game changing indeed! Putting into action with advice to a friend on our Cancer Patient Lab group who is starting Pluvicto. And also supports remopval of the requirement for taxane chemo before Lu177-PSMA. Which never made any theoretical sense anyway IMO. Hugs to you and Ron. Paul

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