CHAARTED Trial - Long-Term Survival Analysis.

[pjoshea13]

New CHAARTED paper below, reflecting longer follow-up.

"In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS)."

"High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis."

"For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone"

An extra 17 months (+50%).

Of course, half of the men do better than median survival. No doubt there will be another follow-up paper.

Unfortunately, "For those with low-volume disease (n = 277), no OS benefit was observed".

-Patrick

ncbi.nlm.nih.gov/pubmed/293...

J Clin Oncol. 2018 Jan 31:JCO2017753657. doi: 10.1200/JCO.2017.75.3657. [Epub ahead of print]

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

Kyriakopoulos CE1, Chen YH1, Carducci MA1, Liu G1, Jarrard DF1, Hahn NM1, Shevrin DH1, Dreicer R1, Hussain M1, Eisenberger M1, Kohli M1, Plimack ER1, Vogelzang NJ1, Picus J1, Cooney MM1, Garcia JA1, DiPaola RS1, Sweeney CJ1.

Author information

Abstract

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

PMID: 29384722 DOI: 10.1200/JCO.2017.75.3657

[eggraj8]

Thanks for this. Do you know of any research on the effect of using Docetaxel for more than six cycles? I will have my 18th infusion next week and I see no reason whey these men quit at six cycles except because that was the test goal.

[dockam in reply to eggraj8]

I did 15 Taxotere sessions in 2015 and got from 840 to 0.7 with a nadir of 0.1in 2017. I'm glad that your MedOnc is allowing you to go over the normal 6 protocol. My MedOnc consulted with a Tumor Board and no one said to offer more chemos, so he left it up to me.

Randy

[pjoshea13 in reply to dockam]

eggraj8,

You might want to look at a thread I started a year ago (there were 5 replies):

"Docetaxel, Total Number of Cycles & Overall Survival"

But see below for what I posted.

-Patrick

New study below [1].

"The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median {overall survival} was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group."

"Treatment with 8 or more cycles of docetaxel was associated with superior {overall survival} (hazard ratio [HR], 1.909 ...), irrespective of lenalidomide treatment (HR, 1.060 ...)."

"Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior {overall survival}; patients who received more than 10 cycles had a median {overall survival} of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median {overall survival} of 22.8 months"

...

In a Hong Kong study from 2015 [2]:

"In multivariate analysis, eight cycles or more of chemotherapy [hazard ratio (HR) = 0.151 ... {was an} ... independent determinant of {overall survival}."

However, in a 2012 analysis of the TAX-327 & CS-205 trial [3]:

"A survival benefit was not detected with >10 cycles of {docetaxel plus prednisone} in men with mCRPC in this retrospective hypothesis-generating analysis."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/275...

[2] ncbi.nlm.nih.gov/pubmed/261...

[3] ncbi.nlm.nih.gov/pubmed/217...

[BigM62 in reply to dockam]

Dockam were you stil hormone sensitive when you did 15? What finally made you stop? Im on 9 and MO says to keep going if i want. I feel good and it has to be helping. But psa is undetectable already and i worry im just pushing faster toeards hormone resistance? Im 55 with extensive spine mets.

[dockam in reply to BigM62]

Yes, still hormone sens and maybe still am. Last chemo on 12/17/15 and started Metformin in 01/2016 and got to 0.2 in August. It got to 0.5 a few months after, started Ursolic acid, resveratrol and curcumin and got to 0.1 a few months ago. I stopped ADT at 30 months- to not get resistant and now we're waiting until PSA is over 2 then restart it.

Randy

[Dan59 in reply to eggraj8]

Anyone who can do 18 cycles is one tough hombre! I did 12 last year , so I know what that is like. Getting ready to try Javenta in a few weeks

[Jscjac]

Hi, Patrick ! Thanks for ALL of your informative posts. I am ever so grateful that you share this wealth of information. I seem to remember in one of your posts, you spoke about finding a rad-oncologist who was willing to do radiation on your bone met. Could you tell me a bit more ? My husband has 5-7 bone mets (two on one rib and five on various vertebrae) and we are trying to decide whether to pursue radiation to those mets. He is in NO pain whatsoever at this time. Gleason 8, RP in Sept. 2017. (Four lymph nodes removed/ two had cancer). Had first injection (Eligard) two weeks after RP. Urologist/surgeon said nothing to be done except ADT. Our reading/research led us to believe otherwise. We have subsequently moved his care to Vanderbilt and have a great MO. He has had an Axumin scan that revealed the aforementioned mets. (Scan was done last week and the spots were described as "very low activity/they did not "light up"; MO says it is reasonable to belive they are prostate cancer because of his PSA level and pathology, etc.) The consensus of the Tumor Board is for Jeff to continue ADT and add Zytiga. (He had his second injection [ Lupron] last week while at Vandy for his scan.) PSA was tested (first time since RP) and was .9 (This was done on Jan. 4 at Vandy). When tested three weeks later, it was .7. Sorry to be ALL over the map, but we have read until we are cross-eyed, and still don't know what direction to take. We DO know that Jeff is young (61) and SUPER-healthy, except for the whole Stage 4 (aggressive) prostate cancer thing. We have indicated, from DAY ONE, that we want to be VERY aggressive in terms of his treatment. Thanks again for all you do.

[pjoshea13 in reply to Jscjac]

Hi jscjac,

I think that most doctors feel uncomfortable straying from standard protocols. However, a good doctor will be willing to discuss departures from protocol, if the patient is well-informed & not a pain in the rear.

When I brought up the subject of oligometastatic treatment, my doctor said that I needed to speak with Dr. X. Evidentally, he was the local radio-onc most likely to agree to treatment.

We had a one hour meeting which was very constructive. He agreed that it was reasonable to treat the lesion at L5. He did point out that there were no studies, so no proof that this would affect overall survival.

Later, during treatment, he said that he was surprised that I had not been in pain. And he also said that I had been at high risk of a fracture down the road. That reinforced my view that treatment of spinal mets is desirable.

Best to your husband,

-Patrick

[Jscjac in reply to pjoshea13]

That is the thing, isn't it ? Balancing the "being informed" and NOT being "a pain in the rear". We are both mild-mannered introverts, so not much danger of the latter. Lol ! Thanks again for your input.

Warmest regards,

Julie

[Hidden]

So I have 50-50 chance of living 57.6 months. I wonder why this study didn't give a median survival time for low volume men? As usual, I'm confused.

[pjoshea13 in reply to Hidden]

Note: OS was "47.2 months for ADT alone".

For the entire study, 513 of 790 men were high-volume - 65%. Considering that OS for the ADT-only high-volume men was only 34.4 months, I back into a bit over 72 months median OS for the low-volume men. Whatever that number is, the addition of chemo did not improve it.

So, IMO, for a low-volume guy - chemo or not - there is a 50% chance of doing better (perhaps much better) than 6 years. Perhaps someone else will check the math.

-Patrick

[Hidden in reply to pjoshea13]

Again, thanks Patrick.

[Dan59 in reply to pjoshea13]

That would put me out to the right surfing the tail of the curve ,being dxed with high volume 140 months ago, And i get another 33 months for doing more than 10 docetaxol, Thanks Patrick!

[AlanMeyer in reply to pjoshea13]

I have to wonder if the failure to improve overall survival for low volume patients was due to no positive effect from chemotherapy, or simply due to the fact that median follow-up was only 53.7 months. Perhaps the low volume patients were living long enough on Lupron alone that any change in OS was not (yet) significant over the observed time span.

I was also surprised that "ADT alone" was described as one of the options. I thought that men who were initially treated with ADT were given the option of adding docetaxel if and when their disease progressed to the point of threatening their lives. In other words, the comparison was ADT + docetaxel vs. ADT followed by docetaxel - which was the standard of care before CHAARTED.

They say that medicine is not an exact science. Fair enough. But it also seems that medical writing is not an exact science - and unfortunately, I guess that's fair enough too.

Alan

[pjoshea13 in reply to AlanMeyer]

Alan,

When I saw that the study was a long-term follow-up, but read of a: "median follow-up of {only} 53.7 months", I did wonder whether a benefit might ultimately show up in the low volume guys. But statistics can be tricky. How long do we have to wait to get confirmation of no benefit?

And then there is that definition:

"High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis."

You are either high or low - no in-between. No transition from amazing benefit to none at all.

It's very odd.

-Patrick

[Shooter1]

Just had #8, added Dexamethasone pills acct. peripheral neuropathy and sloughing skin on back. Still juggling drugs and pressing on hard...Fast growing invasive is nothing to ignore. Added Xtandi last time, after 5, then 6th tests came back and showed improvement.. &7th test results weren't all in today. Waiting can be hard... looking for then tomorrow.

Doug

[Litlerny]

Thanks for the update PJ. I’m one of those low volume oligometastatic guys who is blessed to be still hormone sensitive. I’ve been on Lupron or Eligard + bicalutamide for nearly 3 years now with undetectable PSA all along. Just finished my 4th (of 6) infusion of docetaxel last week as an adjunct. Now wondering if doing the chemo is a waste, and if I’m putting up with the toxicity and side effects of the chemo for no appreciable benefit in OS or PFS. Only time will tell, I guess.

[j-o-h-n]

So Patrick, Iv'e always wondered what you were when you were a civilian?

Good Luck and Good Health.

j-o-h-n Friday 02/02/2018 4:52 PM EST (Ground Hog Day)

[pjoshea13 in reply to j-o-h-n]

Thanks J-o-h-n!

Until 18 years ago I was designing/building systems for an actuarial consulting company. Such as a pension calculator utility. If I survive another year, I will have been studying research papers longer than I was in that job.

Best to you, -Patrick