EXTEND - Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

[pjoshea13]

The results of the EXTEND [EXTernal beam radiation to Eliminate Nominal metastatic Disease] Phase II Trial were published in JAMA Oncology this month [1].

{However, many will have seen the results, as presented at ASTRO 2022, & posted by Fish, 6 months ago [2].}

Results

"The study included 87 men (median age, 67 years ...). ... with 5 or fewer mets.

"Median follow-up was 22.0 months (range, 11.6-39.2 months).

"Progression-free survival was improved in the combined therapy arm (median not reached) compared with the hormone therapy only arm (median, 15.8 months;... 13.6-21.2 months) ...

"Eugonadal {progression-free survival} was also improved with {metastasis-directed therapy} (median not reached) compared with the hormone therapy only (6.1 months ... 3.7 months to not estimable)

{Note that the bar for eugonadal (normal production of) testosterone was set very low at 150 ng/dL.}

"Flow cytometry and T-cell receptor sequencing demonstrated increased markers of T-cell activation, proliferation, and clonal expansion limited to the combined therapy arm."

-Patrick

[1] jamanetwork.com/journals/ja...

[2] healthunlocked.com/fight-pr...

[NPfisherman]

Saw the EXTEND trial information put up on another forum recently...

I have seen a poster state that they are treating the sources of PSA and claiming no cancer progression based on PSA... Ummm, yeah... they are treating the tumor(s)... Does someone else know of any other way to monitor our disease besides PSA and scans?? What that person is ignoring is the increased T cell activity and the previous trials like STOMP and ORIOLE... let's not forget the delay in TTP and median OS...

Proving an increase in OS will take a 10 year study... This is a fact... so why harp on the fact that it hasn't proven an increase in OS??

Thanks for noticing my prior post from 6 months ago, Patrick...

If you are reading this and are an oligometastatic patient, then doing this treatment regimen just makes sense.. decrease tumor burden and if you are MCRPC, remove resistance and decrease the transmission of resistance via tumor mRNA...

So called "experts" that poo poo using SBRT to mets are doing a disservice to the community, and ignoring the results from multiple other trials... Life at eugonadal testosterone levels is good... Feel like your old self...

As the treatment paradigm continues to evolve, we will see SBRT and ADT be given with an immune enhancer/ T cell stimulator is what I suspect will be the next step with an even better response... maybe something like this:

sciencedaily.com/releases/2...

The Science is Coming, folks... so keep them peepers open...

Don Pescado

[Cooolone in reply to NPfisherman]

Awesome info!

Thanks for posting

It is amazing how you guys keep up with this, I find it harder and harder as I think or find so many branches and directions therapy is going these days. Again, thank you!

[NPfisherman in reply to Cooolone]

Cool,

You are most welcome...It is part of our friendly service here at the FPC forum... Indeed, the ability to keep up is getting harder as the treatment paradigm is changing so fast... MO's are not waiting for Phase III trials necessarily to change the treatment plans..

Exciting times...

Fish

[Cooolone]

Thanks for posting!

Was my question and argument back in 2018 when I was persistent PSA post first line therapy (RP), why we weren't specifically targeting any spots which revealed themselves via scans. But Oligo targeting therapy was really mainstream then. Well, fast forward to this past year, in 2022 and I failed my 4th line of therapy and we went after those spots aggressively. A major paradigm change I believe to the thinking as noted about debulking whatever is found outright! Then let systemic therapy do its job for remnant/unseen cell/tissue (cancerous). Is crazy because post Chemo, all scans revealed NO Activity Found... Then 1 year later BAM! We're Baaaaack! Lol

Anyways, I believe "Whack-a-Mole" therapy has definite benefit in given settings. Of course the conundrum is finding who FITS that setting.

[podsart]

Great post, as always Patrick. I think the metastatic directed therapy [MDT} can be viewed as "whack-a-mole" as discussed in many previous posts or one can take the view its a form of controlling tumor burden. Yes, you cannot eliminate the all the sites, as there may be many not detected yet, but destroying major PCA centers to reduce tumor volume can have a value by itself. Buying time [hopefully with some minimum of QOL], for our non curative disease as ours, is the essence of our game. Future tumor burden = Current tumor burden X Pca growth rate, in some complex manner. Unfortunately, location of the tumors plays a role as I understand some locations cannot be treated or very risky.

This idea of including "intermittent therapy" brings to mind my recent post inquiry. I cannot access the full articles of some of the links provided, so its not clear how the frequency of the "on/off" HT is applied. Is it fixed in some form of time frequency or perhaps frequency is a function of PSA level. For example, a number of our members have used trying to keep the PSA at a certain level, not necessarily at undetectable. So, using a PSA[level X] apply ADT till get PSA [1/2 level X], and so on. The hope is this alternating pressure on the Pca will minimize the Pca adapting and killing off the HT sensitive cells, leaving the most ADT resistant cells, with the resultant poor prognosis.

My post asked about a strategy of using a continuous "backbone" of an androgen blocker, i.e., Xtandi, Erleader, Darolutamide] together with an intermittent ADT strategy. Perhaps adding a MDT can further enhance the potential benefits of this strategy. According to my Dr, Firmagon was best suited for the intermittent ADT, in a true clinical setting.

[treedown]

I was going this route until my RO determined that the location of one of my mets was too risky and it was all or nothing deal. I see him again next week to discuss radiation for gynecomestia and will discuss with him further. It felt a little a hail Mary that was taken away even though I was on the fence at the time.

[Brysonal]

Great thread. My first RO was very in favour of SBRT when I had two skeletal mets T1 and third rib and my second RO took on the met at T9 that was proving most stubborn despite Lu-177, chemo and ADT. It’s a heterogeneous disease they tell us but then say stick with ADT which they know fails eventually.

I understand we don’t know for sure if MDT makes any difference to overall survival but we don’t know it doesn’t and there’s are indicators for some it does. It’s low side effect ( in my case) so I will carry on whacking moles if I need to in the future!

10 months undetectable PSA for me. Next bone scan at start of May and discussion with Finland MO. London MO not against intermittent hormone therapy but would rather I stayed on for another year before the conversation.

No idea if my OVM-200 vaccine might have worked .

Great post, the negativity surrounding MDT results from other posters astounds me when nobody knows anything for certain except ADT will fail eventually.

[NPfisherman in reply to Brysonal]

We do know from trials like EXTEND, STOMP, and ORIOLE that MDT via SBRT in oligometastatic disease delays TTP, increases median OS, and shows increased T cell activity and can allow patients to delay the start of ADT or allow a vacation... Continuous ADT that some preach to all is a tough row to hoe as they say in the country.... lol...

Everyone's case is different, but for oligometastatic disease, this seems to have a real advantage when it can be done safely...

Glad to hear of your PSA "undetectableness"... your plan seems to be working well...

All the best,

Fish