The triple therapy consists of ADT+Abiraterone+Docetaxel and is often used for patients who present with bone metastases. In the PEACE-1 trial this triple-therapy showed to be surperior over ADT+Docetaxel (but not over ADT+Abiraterone). The trial showed an overall survival of 61 months for these patients. urotoday.com/conference-hig...
The TITAN study for Apalutamide was terminated after 44 months. The overall survival in the placebo group was 52.2 months while more than half of the patients treated with Apalutamide were still alive at that time and therefore there was no result for overall survival for this therapy. But it was determined that Apalutamide was significantly more effective than ADT alone and therefore the trial achieved its goal and could be terminated. urotoday.com/conference-hig...
At the ASCO GU conference 2024 Dr. Neeraj Agarwal presented the results of a statistical extrapolation analysis of this TITAN study estimating median overall survival of metastatic hormone sensitive prostate cancer (mHSPC) patients treated with apalutamide versus placebo. As mentioned above most of these were still alive when the trial was closed. Dr. Agarwal's result was an overall survival of 71 months, ten months more than the triplet therapy - plus no chemo required! urotoday.com/conference-hig...
Therefore I see no need for the triplet therapy, ADT+Apalutamide without chemo may work even better.
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I think a lot depends on the number of metastases. In a patient who has a very extensive disease it makes sense to do the triplet. Each person is a case apart.
No. One can't compare one randomized trial to a different one with a different patient group.
In the ARASENS trial (docetaxel + darolutamide + ADT) the median overall survival was not reached after 60 months, with no signs of diminishing.
An updated, subgroup analysis of the ENZAMET trial among newly diagnosed men with metastases confirms the triplet of ADT+enzalutamide+docetaxel increases survival. 5 year survival was 60% for the triplet vs 52% for ADT+docetaxel. The benefit was especially pronounced in the first 2 years of triplet therapy in men with high volume metastases.
I'd guess that the addition of docetaxel to triplet adds about a year to overall survival, no matter what ARSi is used with it.
I can't think of any reason that triplet works for abiraterone, enzalutamide, and darolutamide but not for apalutamide, can you?
TA, I wish you can be patient with me and explain to me my situation here as it applies to this discussion because I really don’t understand this overall survival and benefits stuff on how it applies to patients:
I have been on vacation twice .
1) This first time was only given ADT alone ( Firmagon) for a year then stopped. After one year of vacation , my testosterone recovered and I had a Psa of .04 after it had been undectable for the whole vacation year
2) This second time , I was given ADT + Erleada for 6 months . After one year of vacation , my testosterone recovered and I had a Psa of .04 after it had been undectable for the whole vacation year
TA, do you think I should go back on ADT+ Erleada now or wait untill Psa gets high enough to find lesions and treat with SBR if safe? I know your opinion though about MDT that it does not accomplish anything. Thanks.
Thanks for this clarification, Tall_Allen. Was the study focusing solely on the triplet with ADT + enzalutamide + docetaxel? Can enzalutamide be replaced by darolutamide here without impacting on the overall survival rate of 60% at 5 years?
Darolutamide is better, it has the same efficacy and does not cross the blood-brain barrier, so it has fewer side effects. And in any case they also did a study with darolutamide called the ARASENS study and the results were very positive.
The combination of ADT+darolutamide+docetaxel was tested in the ARASENSE trial. You can make a triple therapy with darolutamide as well. ascopubs.org/doi/10.1200/JC...
An updated, subgroup analysis of the ENZAMET trial among newly diagnosed men with metastases confirms the triplet of ADT+enzalutamide+docetaxel increases survival. 5 year survival was 60% for the triplet vs 52% for ADT+docetaxel. The benefit was especially pronounced in the first 2 years of triplet therapy in men with high volume metastases. Enzalutamide is not approved for triplet therapy -- only abiraterone or darolutamide.
The trials using triplet therapy compared ADT+Docetaxel with ADT+Docetaxel+ARSI. It is not a surprise that in this comparison the triplet therapy is more effective than just ADT+Docetaxel.
But these trials provide no information to compare ADT+ARSI with ADT+Docetaxel+ARSI. A trial testing this would most likely show no significant difference in overall survival. Apalutamide is very effective and does not need to be combined with Docetaxel.
I think you can trust Dr. Neeraj Agarwal's analysis of the TITAN study resulting in an overall survival of 71 months. Using Apalutamide would be no mistake. But it would avoid the side effects of the chemo with docetaxel.
Unfortunately Apalutamide is approved in non-metastatic CRPC but not in metastatic CRPC.
If you are interested in metastastasis directed therapy in CRPC, take a look at the ARTO trial: ascopubs.org/doi/10.1200/JC... This is a chart für progression free survival from this trial.
I am in Italy and I know several people who have metastases and are taking it. It has basically taken the place of abiraterone because according to most oncologists erleada is superior to zytiga. I am sure that soon darolutamide will also be approved for patients with metastases.
In this forum I want to recommend drugs for indications that are FDA approved. Apalutamide was approved for non-metastatic HSPC based on the results of progression-free survival. To get approval for metastatic CRPC you would need a trial that shows improvement of overall survival, which will again cost a lot of money. However, I see no reason why it should not work in metastatic CRPC.
Darolutamide has fewer side effects than Apalutamide. But that does not mean, it is more effective than Apalutamide.
In Europe apalutamide has been approved for metastatic patients after the excellent results of the TITAN study. I would be very surprised if in America it is not approved for metastatic patients.
This approval is for metastatic hormone-sensitive PCa, not for metastatic castration-resistant PCa. My initial post was refering to metastatic hormone-sensitive PCa.
Currently had third T injection under Transformer Trial. Last med was Nubeqa. Maybe Xofigo plus Nubeqa is the right combo? I'll also see if Medicare will allow a switch to Apalutamide.
For the last few years bone mets appeared on spine, hips, ribs and pelvis despite being on Orgovyx and Zytiga, enzalutimide and Nubeqa. Definitely resistant.
Xofigo or Radium 223 is a radiation of the bone mets similar to Lutetium. One does not exclude the other. It will work if you are castration resistant. In Melbourne they conduct the AlpaBet trial but you could get Radium 223 outside of a trial in the US: petermac.org/component/edoc... or NCT05383079. In Germany there was the Ralu trial: urotoday.com/conference-hig...
Probably, but it is not FDA-approved for that. I assume that it would work as well as enzalutamide in a triplet in the PRESIDE trial, but we lack data.
If you want to switch to a different ARPI after Abiraterone, I would not switch to Enzalutamide but to Apalutamide: aacrjournals.org/clincancer... However, they could use Apalutamide for that in this trial but to my knowledge it is not FDA approved for M1 CRPC.
When number of metastases triplet therapy Adt(Firmagon or Orgovyx)+Docetaxel+Nubeqa is definately the best treatment you can now get! I got it.Fortunately.🙏And happy to live in Finland🇫🇮,scandinavia. Nubeqa 4,50€/month,Firmagon 4,50€/month and docetaxel (chemotherspy)40€/injection.
This is fantastic. Not only are you Finn's the greatest rally car drivers but your also great at saving our lives hopefully. Please keep updating us all and thanks.
I was diagnosed in April 2024 with advanced PC and numerous bone mets. Gleason 9. I lit up like a Christmas tree on scans. Started treatment in a clinical trial with Doublet Therapy of Firmagon and Erleada. I also had the option of going for Triplet but the clinical trial seemed compelling. I’ve fortunately had very good success with the doublet therapy. Almost all bone mets have decreased and PSA is down to 0.1 and has stayed there. The clinical trial was going to randomly select after 6 months who would stay on doublet therapy and who would just take Erleada. I was not ready to take a vacation from the ADT shot as my MO recommended to stay the course with ADT plus Erleada. I know a lot more about PC now than when I first had to make a decision on treatment. If I had to do it all over again would probably have chosen triplet therapy to begin with. My hope is to remain castrate sensitive with current treatment and then pull out the big guns when PC becomes resistant. Hardest part of doublet for me is brain fog and hot flashes at night. Good luck and Happy New Year to all.
No the two we had at the time were against it. Got the scrip from husband ‘s urologist who also does Biote hormone therapy. He had never written one for this before so I sent him a couple studies I got from janebob on this site and then he was agreeable.
But now we are back to seeing MO Dr Bryce and he was ok that he is on it. Estradiol just checked and was 93. Target is 100.
We had seen him at Mayo in Phoenix so husband was already a patient. But it was easy to get him at City of Hope. We have quarterly appointments. Really like it there. Very coordinated and well run has been our experience to get all labs and scans in one place.
Thanks! Dr Bryce is who we initially wanted my husband to see at Mayo, but we couldn’t get in to see him in a timely manner, and then he moved .( my husband is seeing another MO at Mayo)
I was hoping we could have a second opinion consult with him . (My husband’s treatment plan may need to be changed due to cardiac issues.)
"would probably have chosen triplet" - do you mean adding docetaxel to ADT+Erleada? If your PSA is down to 0.1 now what do you expect from adding chemo to ADT+Erleada?
The TITAN investigators found that the results of the Apalutamide therapy did not differ when the patients had received docetaxel before entering the trial. Therefore adding docetaxel does not improve the results of an Apalutamide therapy.
"The effect of prior docetaxel (DOC) treatment on efficacy and safety of apalutamide (APA) plus androgen deprivation therapy (ADT) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) from TITAN" ascopubs.org/doi/10.1200/JC... - from this article: "Conclusions: Prior use of DOC in pts with mCSPC did not further improve clinical benefits of APA + ADT in TITAN"
Dr Bryce said today he expected husband to get several good years with just ADT and Aptalutimide. It’s only been one year but so far so good and hope he’s right—Scans showed improvement in that mets have shrunk and no new ones. PSA slowly lowering and now to .8. And he said in 4-5 years there would be so much more new in the field to try then if/when the need arises to pivot.
A new meta-analysis comparing triplets to doublets has just been released. Triplet is clearly better than any doublet (including apalutimide) for high-volume disease and is better than the ADT+docetaxel for low-volume disease. The error bars are so large for triplet versus ADT+ARSI with low-volume disease that its not possible to say that one is better than the other. See doi.org/10.3390/cancers1702...
Thank you for the link. The review article coins the terms Docetaxel-based doublet-therapy and ARPI-based doublet-therapy. In the discussion in this thread I think it did not become clear that there are these two types of doublet-therapy. The available trials for the triplet-therapy did compare that with the Docetaxel-based doublet-therapy. But there are no prospective trials comparing the triplet-therapy head-to-head with an ARPI-based doublet-therapy. This comparison is of particular interest because patients could avoid the side effects of Docetaxel if the triplet-therapy results would be about the same as the ARPI-based doublet-therapy. I opened this treat because I came to the conclusion that an ARPI-based doublet-therapy using Apalutamide is even better than a triplet-therapy.
In the cited review they group the ARPIs (Abiraterone, Enzalutamide, Apalutamide and Darolutamide) into one group. This implies that all are equally effective, which I doubt. Anyway, they found that a triplet-therapy is better than a Docetaxel-based doublet-therapy. I never put this in question and this is no surprise. Regarding the ARPI-based doublet-therapy the cited review reports the following results regarding overall survival (not progression free survival):
- For the patients with high-volume disease (n = 9504), triplet therapy did not show a statistically significant improvement compared to ARPI-based doublet therapy
- Among the patients with low-volume disease (n = 9504), triplet therapy was associated with [...] no statistically significant improvement [...] compared to ARPI-based doublet therapy
So they determined no improvement in overall survival by triplet-therapy compared to ARPI-based doublet-therapy. Only the side effects are increased. In the summary and the discussion section this review just concentrates on progression free survival (PFS) because they found a difference there. But overall survival is the main endpoint which you should use when comparing treatments. PFS is usually defined different in trials. It could include PSA progression, progression on imaging, progression to next systemic treatment etc.
I have to point out that the TITAN trial, which is the only trial that tested Apalutamide in metastatic hormone-sensitive PCa, did not report the length of overall survival for Apalutamide. Therefore this review could not include that in its calculations. But Neeray Agarwal took the TITAN data and used statistical calculations to estimate the overall survival. This resulted in 71.8 months, almost 6 years, which is far better than any triplet-therapy.
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