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ASCO 2023 | What is the role of CDK4/6 inhibitors in early breast cancer?

Michael Gnant, MD, FACS, FEBS, Medical University of Vienna, Vienna, Austria, gives an overview of current CDK4/6 inhibitors in early breast cancer. Recent trials such as the Phase II NATALEE trial (NCT03701334) of ribociclib plus endocrine therapy, the Phase II monarchE trial (NCT03155997) of abemaciclib and the Phase III Penelope-B trial (NCT01864746) of palbociclib have all demonstrated promising results. Prof. Gnant additionally talks on the PHERGain trial (NCT03161353) of dual HER2 blockade in early breast cancer. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL.

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Transcript (edited for clarity)

Very clearly the there were not too many pivotal results in the field of breast cancer...

Very clearly the there were not too many pivotal results in the field of breast cancer. There were a lot of interesting contributions. I think most awaited were the results of the NATALEE trial. That’s an adjuvant trial of the addition of ribociclib to standard endocrine treatment. And because we have results from large trials from the two other available CDK4/6 inhibitors, actually controversial results because the Penelope-B and the PHERGain trial did not demonstrate the benefit for the addition of palbociclib, whereas monarchE demonstrated that the addition of abemaciclib will yield sustainable benefits for patients. Also over time and the third CDK4/6 inhibitor ribociclib was tested in this NATALEE trial. And in these very early results, we saw very promising signals. And that’s important also because NATALEE included not only patients at highest risks, but also somewhat limited [risk]. I would call that intermediate risk. So potentially, if these results are confirmed with longer follow up, that could extend the target population of that benefit to, let’s say, maybe 30 to 35% of all breast cancer patients, which is great news in terms of who can benefit. On the other hand, it also raises questions because, for example, when you have a like a 25% relative benefit, this will translate into different magnitudes of absolute benefits depending on where you are on the risk scale. So in the high risk population, for example, monarchE demonstrated the 6% absolute benefit, which is something that most of us will consider worthwhile and and important to go for patients with that composition of risk factors in a node negative population, the same relative benefit might translate into, let’s say, 2% of absolute benefit. And then obviously there is a number of patients that are raised and that’s what currently being discussed in the scientific community, particularly with these very early results. If this is ending up at 2%, it’s a three year treatment. It’s the side effects associated with it. There’s obviously a huge cost associated with is these 2% then worthwhile to to to go for both from a tolerability but also from an health economic aspect. Too early to tell. Eventually we’ll have to see whether these very early results will be confirmed by future updates. I’m pretty sure that the Natalie trial will be updated at every major breast cancer meeting in the next couple of years. But overall, very good news in in addition to that, I think we saw a lot of interesting research, nothing as pivotal, but there was very interesting information on the impact of ovarian function suppression, for example, particularly important in the US where this treatment is still, I would say, undervalued in in general, but to name another example, for example, in the PHERGain study, it was shown that there is a proportion of patients that can be treated very well with antibody alone without underlying chemotherapy. So it is all around this escalation. Find new treatments, new innovation, new benefits for patients who are at higher risk, but also de escalation, maybe not needing all the treatments we have for patients that might be well off even without those treatments and thus sparing them the patients the side effects and society, the cost of these treatments. And so in that respect, with many interesting contributions, I think that’s also going to to to to be the the general subject of our time these days when we have really come to a very successful overall treatment results but still struggling with specifically identifying who is needing which treatment and who is in need of additional treatment and for whom some of the current treatments. We have maybe left out.