Substandard Control Arm in Recently Published mCRPC trials

[GP24]

Recently there were a number of studies published which did not allow the patients the best SOC in the control arm. I thought, well this could not help these patients a lot and everyone knows this. This trial design determines a better result for the arm testing the new therapy. Here is an article discussing this trend: ascopubs.org/doi/full/10.12...

[Tall_Allen]

I agree, but to play devil's advocate, the other second-line hormonal usually does provide a benefit for at least a time, and those trials allowed crossover to the other treatment if the control stopped working. This can provide equipoise for the randomized patient and the treating physician. So for example, if I'm a patient randomized to get enza instead of Pluvicto in the VISION trial, I might stay in the trial if I knew that I would still get Pluvicto if the enza failed in,say, 4 months, and that was my only chance of getting Pluvicto.

That said, I wish they had allowed Xofigo in the control arm. The control should be best SOC. Pharma-sponsored clinical trials in the US seldom compare the new drug to the old drug, but they should.

[Seasid in reply to Tall_Allen]

Actually I myself would prefer to be randomised into the control arm with Enza with the possibility of crossover to Pluvicto. That would be my preference.

István

[tango65]

I think, this may be a problem in the triple therapies studies where they compared triple therapies against ADT and docetaxel . ADT plus abiraterone have a longer median overall survival than ADT plus docetaxel .

IMHO they should have compared triple therapies against ADT plus abiraterone.

urotoday.com/conference-hig...

nejm.org/doi/pdf/10.1056/NE...

[mperloe]

The Institutional Review Board (IRB) is supposed to address issues regarding the protocol and whether the SOC is truly SOC and not a substandard of care.

[Seasid in reply to mperloe]

That is a big risk and headache to the patient. All of this makes very challenging to the peatiant to make a decision/ commitment to participate in any clinical trial as we just don't know. And if you lose your flexibility to make treatment decisions it makes everything even a bigger nightmare. I am not knowledgeable enough to make an informed decision for myself. That is one of the reasons that I am hanging around this board to feel more comfortable with my treatment decisions. You never really knew what is the best for you. You can just hope and have dreams.

[TomMaloney]

My oncologist is also sucked in. She keeps referencing the VISION trial. Is the answer to disregard all company sponsored trials? So now I don't know WTF to do.

[Hidden]

Such an interesting article! It doesn't surprise me that "Only industry-sponsored trials used this control arm" (using Enza or Abi after one or both of the drugs have already been used), with the implied reason that their for-profit treatments will look like better options.

The article states "The academically sponsored phase II TheraP trial did correctly compare radioligand therapy with Lu-PSMA with cabazitaxel." Pluvicto is the newest treatment everyone is excited to try after progression and is actively discussed here. However, there is very little mention here about overall survival being statistically the same as using cabazitaxel.

[GP24]

The advantage of Pluvicto is that the therapy can be repeated. In the study below, patients retreated with Lutetium had an overall survival of 14.8 months compared to 6.6 months for systemic therapy instead. See the poster below from ASCO GU 2023.

Also, following a Pluvicto therapy you can use cabazitaxel. This sequence should work longer than each therapy alone.

Poster describing results of Lu177 retreatment

[GP24]

Novartis reports a successful PSMAfore trial. These CRPC patients got Pluvicto and had no chemo yet. The control arm was a change in (cross-resistant) androgen inhibitors.

novartis.com/news/media-rel...