Article: Transcript: What are the AMEERA-6 Results? A breast cancer study evaluating Amcenestrant or Tamoxifen – David Cameron, MD @EdinburghUni #ASCO22 #OncoTwitter

 

Article: Transcript: Question – Please Tell Us About The AMEERA-6 Trial

 

So, I’m talking about AMEERA-6 which is a trial which is currently ongoing so we don’t yet have any data that reports on the relative activity of the two arms but let me describe the trial to you because this is a trial for patients men and women with potentially curable hormone receptor-positive breast cancer who are currently being treated or have recently had to stop 

 

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treatment with an aromatase inhibitor because they really are struggling with the side effects all of you who treat breast cancer patients will know that we have a significant minority of women and occasionally men who struggle with the side effects of aromatase inhibitors and often either don’t take the drug and don’t tell us or stop taking it and tell us that and therefore they lose the efficacy of aromatase inhibitors we know from several studies that either side of the Atlantic that if women come off an aromatase inhibitor they do not get the benefit that they would get if they were able to carry it on and in the AMEERA-6 trial such women occasionally men will be randomized between switching to tamoxifen which is a well-established and effective drug in breast cancer or one of the new oral surges amcenestrant (SAR439859)which is a drug being developed by Sanofi who are the sponsor of the study and the study is being run in partnership with the breast international group based in Europe with member groups around the world and the alliance foundation for trials in the US so it’s a joint academic pharma company trial addressing this question can you use an oral surge rather than tamoxifen to get greater efficacy for those patients who are struggling with and may already have stopped taking an aromatase inhibitor due to the toxicity which is a well-recognized problem for some patients with this class of drugs.

 

Question – Common Questions From Your Colleagues?

 

I think the communist question isn’t the context people understand that aromatase inhibitors for some women cause toxicity but the commonest question is why are you using tamoxifen and an oral cert selectively receptor down regulator as the test medicines in the trial and what I think gets forgotten is if you look if one looks at the big 198 trial which was the trial that put Arimidex letrozole on the map because it showed that five years of letrozole was superior to five years of tamoxifen there were two other arms in that study and one of those arms was a couple of years of let result followed by three years of temporary and in the big 198 trial there was really very little difference in efficacy that those women who had five years of letrozole compared to those who only had two followed by three years of tamoxifen and in the clinic we forget therefore that those patients who are struggling with an aromatase inhibitor you try one you try another that actually on the basis of big 198 switching them back to take tamoxifen we have evidence that this is an effective treatment and therefore in the trial we picked tamoxifen because it’s usually better tolerated than aromatase inhibitors as our control arm so at least the women are getting something that we know works and there’s an evidence base for that sequence of an AI followed by tamoxifen and then the randomization is against one of these new oral SERDs both because we have reasons to believe that they are likely to be more effective than tamoxifen and secondly, because there are some data that the oral surge may be more effective particularly in those cancers with an emerging ESR1 mutation now we’re not testing for that prospectively in this study but we will be collecting blood samples so that we can later do an analysis to see whether in the minority of patients in the advent setting who do have an emerging DSI1 mutation profile in blood samples whether in fact they particularly get benefit from the use of the oral third and amcenestrant (SAR439859) there are some other minor questions like you know we are mandating for free menopausal women and for men that they should take LHRHa agonists because they would have needed that in combination with an AI which ones can be used but the key one is really that question around why do we pick a tamoxifen as a control arm and it’s because we have evidence that the sequence of an ai followed by tamoxifen is probably almost as good as five years of an AI and these are women who can’t tolerate five years of an ar that’s the patient group we’re targeting

 

There’s probably one other question people ask in our trial unusually for most of the adjuvant endocrine therapy studies we are allowing women in irrespective of the HER2 status of the cancer most artificial studies pick luminal cancers that’s hormone receptor-positive HER2 negative but we treat hormone receptor-positive go to positive breast cancers with hormonal therapies so why isn’t the same question allowed to be asked in them the answer is because it’s a practical question in the clinic these women to suffer from side effects what is the best therapy for them so we’re also including her2-positive breast cancers provided that they meet the other criteria including being hormone receptor-positive.

 

Question – Will This Affect Clinicians Today?

 

So I think I think the date the trial may itself already influence clinical practice on the basis that we are reminding people that there is evidence for the sequence of amcenestrant (SAR439859) inhibitor followed by tamoxifen as an effective treatment and therefore that should be increasingly used as an option for women who don’t tolerate ais clearly our trial is designed to show that there is an even better solution which is the sequence from the amcenestrant (SAR439859) inhibitor to the oral amcenestrant (SAR439859) it’s a hypothesis we won’t know for a few years whether that is true or not so in the future we may well influence practice the drug is better and gets registered with a sequence of an AI followed by an oral third but before then I’m hoping that people will be reminded that there is an option for patients who cannot go into our trial but are clearly struggling with an amcenestrant (SAR439859) inhibitor and that is to switch them to tamoxifen it works.

 

Question – What Are The Next Steps?

 

The next step is to ramp up opening the study across the world in the US in many European sites and sites outside both Europe and North America enroll the patients because the patients are certainly there in our clinics struggling with the romantic inhibitors so if we can enroll the trial get it running, we can then deliver the answer in a few years’ time as to whether the amcenestrant (SAR439859)estimate is going to be better.

 

Question – Final Thoughts

 

I think the important thing is to remember that our patients sometimes struggle more on aromatase inhibitors than they admit to us and up until now perhaps as doctors, we’ve not always dealt with those concerns as much as we should do because we felt that there aren’t many other options I think it’s important when you see your patients to really find out just how much are they struggling actually just how much are they taking your aromatase inhibitors and that there is an option there is the option outside the trial of sequencing them to tamoxifen but also importantly there is an option of finding a site open with this trial and enrolling in the trial so that we can see whether there’s an even better option and the patient could contribute to clinical research whilst coming off the aromatase inhibitor or that minority who find that too disruptive in terms of their quality of life.