Open main menu ☰
HealingWell
Search Close Search
Health Conditions
Allergies Alzheimer's Disease Anxiety & Panic Disorders Arthritis Breast Cancer Chronic Illness Crohn's Disease Depression Diabetes
Fibromyalgia GERD & Acid Reflux Irritable Bowel Syndrome Lupus Lyme Disease Migraine Headache Multiple Sclerosis Prostate Cancer Ulcerative Colitis

View Conditions A to Z »
Support Forums
Anxiety & Panic Disorders Bipolar Disorder Breast Cancer Chronic Pain Crohn's Disease Depression Diabetes Fibromyalgia GERD & Acid Reflux
Hepatitis Irritable Bowel Syndrome Lupus Lyme Disease Multiple Sclerosis Ostomies Prostate Cancer Rheumatoid Arthritis Ulcerative Colitis

View Forums A to Z »
Log In
Join Us
Close main menu ×
  • Home
  • Health Conditions
    • All Conditions
    • Allergies
    • Alzheimer's Disease
    • Anxiety & Panic Disorders
    • Arthritis
    • Breast Cancer
    • Chronic Illness
    • Crohn's Disease
    • Depression
    • Diabetes
    • Fibromyalgia
    • GERD & Acid Reflux
    • Irritable Bowel Syndrome
    • Lupus
    • Lyme Disease
    • Migraine Headache
    • Multiple Sclerosis
    • Prostate Cancer
    • Ulcerative Colitis
  • Support Forums
    • All Forums
    • Anxiety & Panic Disorders
    • Bipolar Disorder
    • Breast Cancer
    • Chronic Pain
    • Crohn's Disease
    • Depression
    • Diabetes
    • Fibromyalgia
    • GERD & Acid Reflux
    • Hepatitis
    • Irritable Bowel Syndrome
    • Lupus
    • Lyme Disease
    • Multiple Sclerosis
    • Ostomies
    • Prostate Cancer
    • Rheumatoid Arthritis
    • Ulcerative Colitis
  • Log In
  • Join Us
Join Us
☰
Forum Home| Forum Rules| Moderators| Active Topics| Help| Log In

Phase 3 Clinical Trial Results for TAK-700 - Metastatic, Hormone Sensitive

Support Forums
>
Prostate Cancer
✚ New Topic ✚ Reply
❬ ❬ Previous Thread |Next Thread ❭ ❭
profile picture
Jerry L.
Veteran Member
Joined : Feb 2010
Posts : 3197
Posted 7/3/2021 7:58 AM (GMT -8)
This phase 3 clinical trial (SWOG 1216) included 1300 patients with newly diagnosed metastatic castration-sensitive prostate cancer that were randomized to androgen deprivation therapy plus bicalutamide, versus androgen deprivation therapy plus TAK-700.

They say that this trial did not meet the “statistical significance” and didn’t meet the primary endpoint for overall survival, but check these results and video out.

- The median overall survival in the control arm with ADT plus bicalutamide was 70 months. The median overall survival in the experimental arm was 81 months. So there was an 11-month improvement in median overall survival in the experimental arm, with a p-value of 0.040 and a hazard ratio of 0.86, favoring TAK-700. (11 months…I find that very interesting….)

- The progression-free survival was remarkably improved, in fact, it doubled with TAK-700. The median PFS in the control arm was 23 months and the median PFS in the experimental arm with TAK-700 was 47.6 months with a hazard ratio of 0.56 and a p-value of less than 0.001. Even PSA response rates were also significantly higher.

The below article and video talk about this trial and seem to suggest that results might be even better with some of the newer hormone therapy drugs like Zytiga used in combination with TAK-700. (I’m not sure about Xtandi, but would be interesting if this could be a possible combination….).

https://www.urotoday.com/categories-media/2013-centers-of-excellence/mhspc-coe/2215-the-addition-of-tak-700-to-testosterone-suppression-its-effect-on-survival-in-mcspc-swog-1216-neeraj-agarwal.html
profile picture
Tony Crispino
Veteran Member
Joined : Dec 2006
Posts : 8160
Posted 7/3/2021 11:48 PM (GMT -8)
It's important to note that this trial was a potential standard of care changing trial that did not meet that criterial (25% OS improvement over SOC) There are still uses for the drug but it's not clear that Takeda will continue production. Neeraj and I had this conversation when I saw the 81 versus 70. As he says in the video there was not a significant reason to change standard of care. But that while TAK 700 showed a marginal improvement, it is clear that trials seeking to make apalutamide, for example, available in this setting will likely meet that threshold to change standard of care now and at a much more improved level. There were some great points in the 1216 trial, however:

1. The control arm of SWOG 9346 had 46 month OS in the control arm using the same agents. The control arm of SWOG 1216 was 70.1 month. What this shows is that collectively the available home therapy intensification drugs and chemo approaches are working quite well in extending lives for these mHSPC guys. We think if the standard of care today, with modern multiple hormone intensification strategies, was in use in 2012, these patients could have exceeded 9-10 years OS. Which is significantly better than the TAK 700 arm here.
2. This trial was a fantastic data gatherer. We gathered a mountain of bio specimens and molecular information. This information is still being analyzed and SWOG will release more info on it soon. This is excellent data for future targeting approaches and we'll likely see that effect.
3. We helped define use of circulating tumor technology for prognostic reasons.

SWOG is getting ready for upcoming publications on S1216 in NEJM, Lancet, and more. Stay tuned. LOL I'll be co-author to all of these documents should they be published.

The first project I took on when I joined SWOG was S1216 and working on the informed consent form. The life of this trial showed me the painstaking process of taking a trial from concept, through rigorous CTEP review at the FDA, to activation, to accrual, to completion. This has been quite an experience. Still is.

Tony
profile picture
mattam
Veteran Member
Joined : Aug 2015
Posts : 4118
Posted 7/4/2021 4:36 AM (GMT -8)
<< What this shows is that collectively the available home therapy intensification drugs and chemo approaches are working quite well in extending lives for these mHSPC guys. We think if the standard of care today, with modern multiple hormone intensification strategies, was in use in 2012, these patients could have exceeded 9-10 years OS. >>

I like the sound of that! Obviously not for the guys who missed it in 2012, but for those of us currently on that treatment strategy.
profile picture
Jerry L.
Veteran Member
Joined : Feb 2010
Posts : 3197
Posted 7/4/2021 4:55 AM (GMT -8)
Thanks Tony for the behind the scenes look at this trial…Over the years I’ve found the whole process fascinating and unfortunately very slow…but I get that this has to be the way it is to get meaningful information and change.

I’m not very familiar with this particular drug…but if it is still being made in the future…would this be something that might be beneficial if added to as a combination therapy with either Lupron/Firmagon and Xtandi/Zytiga? Only asking because oftentimes these drugs and therapies seem to be more effective in combinations. (Wow…as I typed that…I flashbacked 12 years ago when I was wondering if there was a benefit between taking Lupron vs. Lupron/Casodex, etc…)

Lastly and most importantly….Thank you to all of the hero patients that took part in this trial and to all of the families and friends. I think we had a few on this board, like Sonny3, that were part of it. I was part of just a PSMA imaging trial a few years ago and I understand to a small degree the commitment that is needed. It’s so important that patients consider trials like this…and again…specifically…those that participated in this trial are rock stars.
profile picture
Tony Crispino
Veteran Member
Joined : Dec 2006
Posts : 8160
Posted 7/4/2021 2:32 PM (GMT -8)
Jerry,
First I totally agree with gratitude to all participants in clinical trials. I remember when Sonny and a few other guys I have associated with that were on this trial. Of course all I could do is cheer them on because the purpose of any clinical trial is to answer a question and we had not had these questions answered yet with TAK700.

I brief history of TAK700 in prostate cancer. Dating years back before even we had docetaxel (TAX327 Trial in 2004) we had several potential drugs in regular use. One such drug was Ketocanazole, or Keto for short. Keto worked to some degree by inhibiting the enzymes CYP17,20. The down side of Keto is that it destroyed livers. Researchers looked for better ways to attack this pathway and eventually in 2009 abiraterone acetate cleared with expedited release as a well working Cyp17, 20 inhibitor. It extended lived. On the down side of the drug is the requirement for a corticosteroid. Prednisone. TAK700 was being researched in Japan and could be seen as an alternative to abiraterone. Here is a breakdown of this research:

https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3047603/

TAK700 had failed in demonstrating improved survival in mCRPC patients in previous trials. It was questionable if is would work in the mHSPC setting. Enter S1216. However after these trials all failed, I see a likely end to TAK700 after S1216 for use in prostate cancer.

The STAMPEDE trial showed that abiraterone worked in the mHSPC setting but it came with the need for a steroid. If TAK700 could show a 25% improvement in S1216 in OS in S1216 it would be a reasonable alternative to Zytiga. It did not do so. Thus it was not considered a success. As it is, it was still a great trial that gave us great information. That's what a long and drawn out trial with good design can do even if the experimental drug does not make its endpoints.

Considering the ties between abiraterone and TAK700 both being CYP17,20 attack mechanisms, It is not likely that they could be used together to improve the results. This is one of the Exclusion Criteria of S1216 was:

"Prior or concurrent therapy with ketoconazole, aminoglutethimide or abiraterone acetate, or enzalutamide (MDV3100)."

Simply put these AR drugs would contaminated our trial. And in the end they were disallowed unless progression indicated allowing their use.

Tony

Post Edited (Tony Crispino) : 7/4/2021 4:35:32 PM (GMT-6)

profile picture
mattam
Veteran Member
Joined : Aug 2015
Posts : 4118
Posted 7/5/2021 11:59 AM (GMT -8)
Tony,
If you're still monitoring this thread, I have a question.

Concerning the hormone-sensitive guys with very few identifiable mets. If they started ADT therapy with Lupron + one of the oral ADT drugs (Arbiraterone, Enzalutamide, or Apalutamide), are you saying these guys may have a reasonable expectation for a 9 or 10 year OS?

I'm hoping I understand you correctly.
profile picture
Tony Crispino
Veteran Member
Joined : Dec 2006
Posts : 8160
Posted 7/5/2021 9:14 PM (GMT -8)
mattam,
When this trial began, the trial had flexibility in the use of changing standard of care. There were a lot of trials and treatment options added after S1216 got launched. This includes early intervention trials for docetaxel (CHAARTED), early use of abiraterone (STAMPEDE) and many new agents driven by, but not just driven by, 2nd line hormonal therapies. We've seen new target agents for PD1/PDL1, BRCA, CHEK2, ATM, and even targeting with Lu177 PSMA. What I indicate is that the median was 70 months in the trial for the SOC side which kept improving during the life of this trial. So is it possible that we can see todays standard of care showing in a new Phase III trial a potential median of 9-10 years. Yes I think that's possible. Maybe probable.
profile picture
mattam
Veteran Member
Joined : Aug 2015
Posts : 4118
Posted 7/6/2021 5:37 AM (GMT -8)
Thanks Tony,
That's the most hopeful information I've seen in quite a while.
profile picture
Tony Crispino
Veteran Member
Joined : Dec 2006
Posts : 8160
Posted 7/11/2021 1:33 AM (GMT -8)
Jerry, here is the Phase III results and final reporting on the Titan trial that tested in the same scenario as the TAK-700 trial. mHSPC and mCSPC are the same patients. As you can see TAK-700 had no where near the positive results that apalutamide did. I expect with this reporting I'll see some email coming from another direction through the AUA/ASTRO/SUO advanced prostate cancer guideline panel that we'll agree to recommend lupron and apalutamide to be considered in the care for these mHSPC patients.

https://ascopubs.org/doi/abs/10.1200/jco.20.03488
profile picture
Jerry L.
Veteran Member
Joined : Feb 2010
Posts : 3197
Posted 7/11/2021 4:52 AM (GMT -8)
Thanks Tony.

Is there an equivalent trial for Xtandi. I know of the ARCHES trial, but I think the endpoint was only radiographic progression. Just curious how Xtandi and Apalutamide match up head to head.

https://ascopubs.org/doi/full/10.1200/jco.19.00799
profile picture
mattam
Veteran Member
Joined : Aug 2015
Posts : 4118
Posted 7/11/2021 5:54 AM (GMT -8)
Exactly my question, Jerry. Hope, I picked a good one! 😉
profile picture
Jerry L.
Veteran Member
Joined : Feb 2010
Posts : 3197
Posted 7/11/2021 2:34 PM (GMT -8)
Mattam,

Aside from the studies and trials which look at large number of guys….Over the years I’ve seen a wide range of results when looking at the sequencing of these therapies and I’m sure you have as well. I’ve seen guys do very well on just Lupron followed by the 2nd gen hormone therapies. I’ve also seen the opposite with guys taking these drugs early and being not as effective….and vice versa. It is just so different for everyone and I guess so many different types/variants of PC.

I’m also curious if Apalutamide is effective at all after Xtandi.
profile picture
mattam
Veteran Member
Joined : Aug 2015
Posts : 4118
Posted 7/11/2021 3:46 PM (GMT -8)
Yes Jerry,
I think the shifting of combinations 1st and 2nd line ADT drugs have significantly increased survival by years instead of a just a few months. Plus, throw in Chemo -- that's a lot combinations and permutations. I really hope some non-ADT breakthroughs come soon. Maybe mRNA therapies will help us out.
✚ New Topic ✚ Reply


More On Prostate Cancer

An Unexpected Diagnosis Of Prostate Cancer

An Unexpected Diagnosis Of Prostate Cancer

Positive For Prostate Cancer

Positive For Prostate Cancer


HealingWell

About Us  |   Advertise  |   Subscribe  |   Privacy & Disclaimer
Connect With Us
Facebook Twitter Instagram Pinterest LinkedIn
© 1997-2023 HealingWell.com LLC All Rights Reserved. Our website is for informational purposes only. HealingWell.com LLC does not provide medical advice, diagnosis, or treatment.