Last year, the PEACE1 trial showed that the combination of abiraterone+docetaxel+ADT, all started at the same time, increased survival by over 1 ½ years in men with high volume metastases (we are awaiting data for low volume).
Similarly, the triplet of darolutamide+docetaxel+ADT, started simultaneously, decreased mortality by almost a third.
The first results of the ARASENS trial were presented at the 2022 ASCO Genitourinary Conference. All 1,306 patients treated from 2016-2018 were randomized to receive darolutamide (DARO) or placebo (PBO) on top of docetaxel and ADT. They found that:
• DARO significantly decreased the risk of death by 32.5%
• The survival advantage subsisted even though the PBO group received more therapies later
• The survival advantage was maintained in all subgroups (i.e., disease extent, type of metastases, ALP levels)
• DARO delayed time to castration resistance by 64%
• DARO delayed time to pain progression by 21%
• DARO delayed time to first skeletal event/fracture
• DARO delayed time to next chemotherapy
• Treatment-related adverse events were similar and were highest during the time chemo was given (mainly neutropenia)
• Treatment discontinuation was low and similar in both groups (13.6% for DARO) vs (10.6% for PBO)
Hopefully this will finally put a stop to those who continue to post on this site their personal opinion that PC patients are better off to do treatments sequentially as opposed to early in combination. This was at one time the SOC. NO MORE!!! The facts couldn’t be more clear.
I don't kmow who these people are who are against combination therapy, but you shouldn't get upset (e.g your "NO MORE!!!"). If some of the best minds back in the day preferred to keep something in their back pockets for their patients, how can you fault a patient for thinking the sequential approach best? Dr. Myers exposed the mathematical fallacy of such thinking years ago in a vlog post, although he was talking about durable remissions - not 1.5 years. We have a ways to go.
You write: " sequentially as opposed to early in combination".
How did "early" creep in? I believe that you are a fan of early, but the study did not compare early/later.
Patrick, I hope TA will jump back in. As Schwah said, I believe the studies were all about being early. Right out of the gate-All 3 in combo.When PEACE 1 Trial first came out at 2021 ASCO, I immediately went to my Onco and said I am on 2 of the 3 (Lupron & Abi), I want to add Docetaxel now. He said NO, this was only for Men who start this at Diagnosis. Now, he said your ADT has put PCa cells in Sennescence andy Doxy will not do anything. PCa cells must be active for Doxy to work.
It didnt seem right to me so I asked TA. He said, unfortunately for me, he is right. This all works best if done upfront.
Listen, Patrick, this is not me challenging you. Way too much respect. You hv forgotten more than I will ever know. But this is too important. 1-1/2 years, now lengthening with Darolutimide vs Abi. And we cannot forget less brain fog w Daro.
Sure, the guys were treated early and some are concluding that early is always better but there was no 'not early' arm. Apologies for being pedantic.
The drug companies have their eyes on the much bigger PCa market - the non-metastatic guys. I can see a day when newly-diagnosed nmPCa guys will be pressured to begin a multi-drug therapy at diagnosis, because "early is always better".
When I was diagnosed, there were still doctors who were putting men who failed primary treatment on Lupron. Medicare had removed the profit motive, but it was still happening. Even years later. Perhaps those docs subscribed to the idea that at diagnosis, cancer cells have already escaped the capsule? i.e. no such thing as "nonmetastatic".
About 10 years ago, there was a paper that reported no survival advantage for non-metastatic men to be on Lupron. But, as my doctor noted, an awful lot of unnecessary morbidity in men who were on it for a long time.
I wasn't metastatic at diagnosis, but I was offered Lupron. I declined. That was 17 years ago.
I am 74 now, but at 56, Lupron would be expected to fail by age 58. Abi & Enza & the rest were not around, but a 56 year old would not be impressed by the numbers.
At the moment, we have no curative therapy. When we start using the drugs, the clock starts ticking. If we delay treatment by one month, do we lose a month during treatment? Is time really of the essence?
TA, A) ADT (Lupron) +Zytiga/Abi+DocetaxelB) ADT + Zytiga- No Docetaxel
C)ADT + Docetaxel - No Zytiga
All 3 groups of guys in this string alone. Think how many on this forum just observing?
So many of us diagnosed before Peace 1 Trial. So we are left to wait until Hormone Resistance?
Docetaxel not worth starting for me at PSA .26.
Guess my only option is to wait until failure. Maybe switch Lupron for Darolutimide as less brain fog issues and possibly longevity? Also wait for H Resistance?
PEACE1 was A vs C. It delayed progression by an extra 2.5 years. By comparison, docetaxel+ADT delayed progression by an extra 1.1-1.4 years over ADT alone. Abiraterone+ADT delayed progression by an extra 1.4-1.6 years over ADT alone. So, you see the benefit seems to be additive. There was a similar additive benefit in overall survival among patients with high volume metastases.
Darolutamide was given with Lupron, not instead of Lupron.
Thanks TA,Meant Daro vs Abi. Do u see a benefit of switching to Daro now? Or wait until resistance and try then? I like the idea of less brain fog. Mike
Patrick , you advised me in a message last year to avoid taking Zytiga or longer term ADT if possible , basically because , as you said here, the clock starts ticking . I just had 26 doses of radiation for my high risk ( PSA 61 ) localized non - metastatic (based on PSMA -PET ) PCa and started on 24 months of Orgovyx and Zytiga .When I expressed my concern about CRPC MSK docs said “ we’re treating you with curative intent , that’s not a concern . “ Tall Allen wrote that early use of this regimen does not speed up CRPC onset.What am I missing ?
If I may intrude, the only thing you are missing is that MSK has some of the best, most educated doctors in the world. The "clock starts ticking" once there are metastases, not because you are taking ADT. I hope they are right that you are now cured.
Thanks ! Yes , I feel very fortunate to be in their care. I went up from Baltimore because Johns Hopkins Dr Hahn ( whom you pointed out to me is also world class ) would not treat me without a new biopsy . I had just one biopsy in 2009 read by Epstein who said Gleason 6 with one core of 12 with a little over %50 cancer. I didn’t think I needed a new biopsy with the PSMA - PET results and MSK agreed .
I think it's a numbers game, the lower you get the numbers at the beginning, the less there are later. It's like trapping wasps in the springtime. Every one you kill in the spring eliminates many more in the summer and fall.
There used to be a controversy whether treatments that select for resistant strains (and they all do) is trumped by the reduction of sheer numbers of cancer cells by early use of powerful systemic treatment. All trials so far tell us that early use of our most powerful medicines beats selection pressure very time.
Patrick says the “ the clock starts ticking .” I think you posted a study showing that early systemic treatment doesn’t hasten CRPC . MSK docs prescribed 24 months of ADT and Zytiga for me and said CRPC is not an issue . I just finished 26 radiation doses Friday . Thanks for all your very helpful input .I was reassured when you commented that my treatment plan sounded good awhile back.
Multi-modality seems to throw just a bit too much for the cells to process and counteract at one given time! Is awes me to see these type of results and will be even more awesome that MO's pay attention and incorporate them into benefit for their patients!
I was mid-stream Docetaxel last year when Peace-1 abstract was released and tried talking my MO into starting the additional drug even though I was 3 infusions in (½ way through 6)... I felt that the last 3 with the extra bang for the buck was better than without, seeing how much of a difference adding the additional drug resulted in. But to no avail, lol. And even through this is for nuvo patients, I'm sure those who're 2nd or 3rd line treatment would benefit as well. Absent a RCT to prove it of course, it's just an opinion.
My husband had a very similar experience. He had had 2 treatments with docetaxel when we brought the PEACE trial results to his team. They refused our request as well. He was started on abiraterone in August, but that has already failed and he is now receiving carbazitaxel and carboplatin. We will always wonder if his results would have been better if they had listened to our request.
Myself as well. Finished round 6 of chemo and my MO at the time even mentioned starting Abi then I moved, new MO and finally after 2 or 3 tries over 2 or 3 appointments even mentioning the preliminary Peace-1 findings I said: "So actually you believe in sequencing the treatments, waiting for progression". He nodded in the affirmative. I was hovering around a 8 to 9 PSA for 11 months after chemo before rise and Abi was started. Kind of to add insult to injury now with the great response to Abi these past 6 months it is obvious that while I lived with PSA at 8 to 9 that pain in hips and femurs was not adt osteo effects it was metastases' festering. Still some pain but not as much. I think damage was done.
I've wanted to vent about this for awhile and this looked like my opportunity in this thread so please bear with me lol.
Ironic my first post here was "Is it SOC to not add anything to chemo with a fully metastasized individual" ?
In retrospect I should have posted "Help! I need Abi and I'm not getting it!" lol.
I realize your post was 5 months ago, but wondered what , and especially when you followed up your docetaxel treatment. I am mHSPC diagnosed March and have had 5 of 6 Docetaxel plus Lupron. Hoping to get darolutamide next but worried about when to start.
Your experience , thoughts would be much appreciated.
I wasn't offered any change in direction as noted above in my post. And even though we might think there would be benefit, we really don't know. I'm currently maintaining just ADT (Orgovyx) post Docetaxel &ADT... Of course until resistance!? I'm not sure I would ever take a break, but would be interested in possibly switching things up somehow, adaptive theory, why wait till failure. But also worry about burning lines of therapy. Of course I always wonder if there's something else I should be doing to help or have things working better.
It's a mine field to navigate for sure. We can always second guess but at some point have to surrender and trust our MO's or else what are we doing?
My follow ups have been every 3 months, finished Docetaxel last June and so far, have been so good! PSA <0.05 and T has maintained below 10 (5-8)... So the drugs work, and is working! I hope because my response it stays that way for a long, long time ;). I have upcoming scans to make sure as well.
Thanks for taking the time! Your input is helpful/interesting. Would love to hear significant updates, or changes in the future. I wish you continued success!
I will add to those who were midway through treatment when Peace trial results came out. My MO brought this to oncology committee at Georgetown. Based on their recommendation we stayed with just Doxy and ADT😒. Currently on Xtandi and ADT and last PSA at 6.7. Went up from 5.7 last month so that is concerning. Have PET scan today 🙏 Thanks TA!
Thanks TA for sharing such good news for our brotherhood.
For those of us who started bi-therapy (ABI+ADT), would it be worthy to stop the bi-therapy, wait for PSA to increase (and dormancy to stop) and then knock hard with tri-Therapies ?
TA, would mind looking over how many of us (certainly more than just us few respondents) were half way into our SOC when PEACE 1 first reported at ASCO 2021 on this Triplet upfront in unison approach. Some of us were Lupron+Zytiga No Docetaxel, others were Lupron Docetaxel No Zytiga.What do you feel best now? Just wait for symptoms and get on the sequential train?
If you only had a few docetaxel infusions, that's fine, but if you've been on abi for a while and PSA has been driven down to nearly undetectable, you can't begin docetaxel until there is cancer activity again. Otherwise you would be getting just toxicity and no benefit.
I've been on Lupron/abi/prednisone for 14 months and am undetectable. This was exactly the answer when I posed this to my MO a few weeks ago. Stick with what's working and don't upset the cart. Yeah, the potential extra months when adding the Docetaxel would be nice but I don't mind not having the side effects of the chemo drug.
I run into that attitude from MOs a lot. Consider this: before CHAARTED, your MO would have said the same thing - your PSA might have been undetectable and there were no new metastases -- it's working! Don't upset the cart! But CHAARTED proved that you could prolong your progression-free time and prolong survival by taking docetaxel with the ADT. Since CHAARTED, randomized clinical trials have proven similar benefits for Zytiga, Xtandi, Erleada, and now even more benefit by combining docetaxel with Zytiga or Nubeqa.
Docetaxel provides increased quality of life. Most men find the infusions tolerable, and no one promises it will be pleasant. But after 6 infusions, 3 weeks apart, men who do it report better quality of life than men who don't do it.
One more clarification, if I may. So being on Lupron only for several years (no abi, no enza) doesn't mean you can't now add docetaxel to the Lupron only for a better effect (potentially)? Do I have that right? Thanks again.
SUV was up about 50 per cent on 9/21 PET scan from 8/20 PET scan on all visible Mets. Background uptake throughout body up by similar amount. That's really all I know. Neither of my oncologists seemed phased by those results.
If the cancer was up by the same percent as the background, it could just mean you had a fresher batch of the radioindicator. No PSA increase? No new metastases?
No. PSA has been steady at 0.6 for 2021, the lowest since starting Lupron in 2018. Last PSA in December, next in March.
3 Mets visible now. In 2018 there were as many as 8-10, although there was no certainty that all were mets. My largest met, in my hip, visible since beginning in every scan, was no longer visible on last MRI in September. However, PET scan same week still showed a 50 per cent increase in SUV in that spot.
I've found the whole scan results issue very confusing, and my RO seems puzzled about it too. But treatment has remained unchanged-Lupron only.
Please excuse my ignorance. I am learning as fast as possible.
I am mHSPC, diagnosed 3/1/22, doing Lupron and Docetaxel since March (5 of 6), and MO has mentioned Nubeqa as the next treatment. Given success of triplet therapy, although that used Nubeqa from the start, I was going to ask today to get the Nubeqa started as soon as possible. The risk of cellular senescence appears to kick in quickly after stopping docetaxel. So, if I understand you correctly, you believe the start of Nubeqa (which may be hard to get approved for my metastatic case) is critical even if it takes a couple/few weeks to get approved? My concern is that at this early stage, nothing has had a chance to stop working, and I've read (5/23/22 article from "Prostate Cancer News, Reviews & Views") in the noted article that" When chemo or advanced hormone therapy is used as a monotherapy, protective mechanisms (senescence) kick in soon after. They (Nubeqa, docetaxel, lupron) would have to be used together or wait until the first drug stops working."
It sounds like you disagree, or did I misunderstand you?
I would appreciate your thoughts and hope may question was clear.
I wonder?? In my case I started with SOC ADT+docetaxel. After 20 months there was a sudden change as another castrate resistant form appeared and I went on Xtandi. I reason that this was not active before and had I already been on Abiraterone (or Xtandi in my case) then this flare would not have occurred (it was a sudden outbreak). Since ADT stops production of Testosterone, and Xtandi blocks the receiver on the cancer cell then starting them both together will be a double lockdown - but shouldn't we be comparing ADT/Docetaxel/ abiraterone success in this trial with the numbers from ADT+Docetaxel - followed by Abiraterone started when the castrate resistance appears since in my case the addition of Xtandi after 20 months has put me back on the same PSA downward curve as before Xtandi??
StoneArtist,I believe that is what Patrick was saying above. There wasnt a B or C Group to compare. I am a 3rd category w Lupron + Abi upfront. Now told Doxy wont work as cells in sennescence. So I wait for failure, then try Doxy to put me back in a Hormone Sensitive state.
We are all a giant experiment. If I was diagnosed a year later, I hopefully would have been offered the Triplet therapy.
It would be interesting to compare A vs B vs C at 5 years. It would hv to be a select group as so many other co-morbidities exist (like drinking, smoking, no excercise, overweight, cholesterol, High BP, etc etc).
They did, in fact, look at what happened to the men who did not receive the triplet therapy. They did worse, in spite of receiving more therapies later.
I'm not sure I followed you, but in theARASENS trial, ADT+Doc+DARO delayed castrate resistance and the time to take more therapies. PSA is important but you are mistaken in your belief that because you are on the same "downward curve" as before, your cancer is in the same place as it was before. Unfortunately, it isn't.
My reasoning is that whilst ADT restrains the original cancer tumours untill they are minimal (but still there) the sudden flare of PSA must indicate mutations of castrate resistant tumours somewhere. So I am now in a situation that I have the original PC tumours which are castrate sensitive - and which are being kept down by ADT - plus some as yet unidentified new tumour growth from one - or more of the metastasis which is castrate resistant. So I am now managing two types of cancer (at least). Do I understand this correctly???
There is always a mix of cancer types within any tumor, and castration resistance involves several biochemical changes. ADT will always prevent testosterone from activating the AR - that is true whether the cancer cell is castrate resistant or hormone sensitive.
Thanks, TA. I'll have to read up on DARO, it's new to me.
Meanwhile, I have your earlier PEACE trial account of Lupron, Zytiga, and docetaxel.
Question. I meet with MO in late March to discuss. In the past, he's taken the position that since I started on Lupron only 3.5 years ago, and PSA is at all time low of 0.6, he's reluctant to add either Zytiga or chemo, much less both.
Diagnosed Fall 2018, Gleason 9, PSA 200, at least 3 and up to 10 bone Mets (only 3 visible now), all in hip socket, ribs and spine. Let me know if you need other details.
Get a second opinion. By Fall 2018 we already had CHAARTED that changed the standard-of-care to include docetaxel. He is wrong to think that your PSA is your cancer - it is,unfortunately, a common error.
My just discovered mets are distant (mediastinal & supraclavicular), not all in the pelvis (common iliac), but all 9-10 are in lymph nodes. I'm exploring LU177 options. If I can get that, I'm wondering what to combine with it (hormone sensitive still).
I meet with my medical oncology next week. Should I push for multiple treatment regimen although I am not newly diagnosed..EBRT and brachytherapy 3 years out. After stopping lupron a year ago.
Recent PSMA PET with 4 lymph nodes groin area.
MO started me back on lupron and casodex.
I’m pushing to add zytiga plus chemo.
Doesn’t it seem better to hit the cancer with everything in the arsenal while the cancer burden is low?
But can’t one infer from the trial it could benefit already treated patients. As someone with an aggressive cancer, Gleason 9, I want to stop it from further spreading. If not chemo, would adding zytiga or similar agent help?
Sorry for bothering you. Promise this will be my last post.
Unfortunately, one can't infer that. Treatment and time change the biochemistry of the cancer. What works in the de novo situation may not work later on.
Is this true for triplet Arasens too? This is FDA-approved for men newly-diagnosed with metastases. Does this mean that men with active newly recurrent mHSPC are not expected to benefit from starting ADT+DOC+DARO?
New this week - There was a very small sample (80-90 in each arm) of metastatic recurrent men in the Arasens trial, and there was a non-statistically significant benefit - mortality reduced by 39%. Was the lack of statistical significance caused by the small sample size, too short follow-up, or was there no benefit? IDK. It's worth a discussion with your oncologist.
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Current PCa treatment options in the UK do NOT include Triplet Therapy!
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