Comment: CDK4/6 inhibitors in advanced breast cancer

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Published: 29 Sep 2019
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Prof Nadia Harbeck - University of Munich, Munich, Germany

Prof Nadia Harbeck comments on data from two studies looking at CDK4/6 inhibitors in advanced breast cancer during a press conference at the 2019 ESMO congress.

The MONALEESA-3 trial was looking at treatment with the CDK4/6 inhibitor ribociclib plus fulvestrant in postmenopausal patients and the MONARCH 2 trial looked at the CDK4/6 inhibitor abemaciclib plus fulvestrant in pre-, and peri- and postmenopausal breast cancer patients.

Great data. The two authors said that they’re biased but I think I can also say that I’m not involved in either trial but they’re really clinically highly meaningful data for our patients. You saw by Dr Sledge that 50 months to chemotherapy, this is a game-changer in metastatic breast cancer. But let’s take one trial after the other.
The MONARCH-2 trial shows for the first time a significant overall survival advantage in a purely second line cohort of pre- and postmenopausal patients. It’s the first time we see overall survival data for abemaciclib which is one of the three CDK4/6 inhibitors. The delta of ten months is really clinically meaningful but also the 46 months patients live with their metastatic disease in the second line with abemaciclib.

MONALEESA-3, as Dr Slamon pointed out, rounds the data for ribociclib. It’s a postmenopausal study but they presented earlier another trial at ASCO this year for the premenopausal patients. MONALEESA-3 for the first time gives us now data in the first and second line setting, so patients who have not been receiving any endocrine therapy before that. That makes it also highly clinically meaningful because we were always struggling with whether to give these drugs first or second line. I think now we can see there is a first line survival benefit that that should be the new standard of care – CDK4/6 in the first line setting.

So the data are highly clinically meaningful. I think they’re going to make a huge impact in how we treat metastatic breast cancer. It’s a disease where the epidemiological registries give you a median of 2.5 years median survival and here now you saw in the MONARCH-2 study, which is a slightly later line of therapy, 46 months median survival, that means half of the patients even live longer. And with the MONALEESA-3 data we didn’t even see the median because the patients are doing so well but the control arm was at 46 months. So you can see that that is stretching out quite a bit.

So I think the data will make sure that these drugs are going to be standard. They should be, in my opinion, first line standard in the metastatic setting because you can never guarantee that the patient comes back for a second line of therapy. They may be too sick, they may not want to come back so we should give the best drugs first. The overall survival differences are also meaningful for access to these drugs because some of the health technology assessments in the individual countries around Europe do require overall survival for reimbursement so this data is going to change that.

Lastly, and I will stop there, Dr Slamon was one of the pioneers of the HER2 story and he cannot say that but I think that these drugs will be a similar success as the HER2 story for our patients with hormone receptor positive breast cancer. These drugs will need to be explored and they already are doing that in the early breast cancer setting because there we cannot just prolong survival but reach cure and these trials will hopefully reach out and be presented in the next year or two and hopefully also at the ESMO meeting. Thank you very much.