CDK4/6 inhibitors for metastatic breast cancer
Dr Giuseppe Curigliano - European Institute of Oncology, Milan, Italy
It’s an emerging field, I believe, that is changing the landscape in the treatment of metastatic breast cancer. Specifically you have now the opportunity to candidate many more patients to CDK4/6 inhibitors rather than to chemotherapy. So if you have visceral disease and you have an ER positive disease it’s no more opportune to propose chemotherapy because we clearly listen from the data from the MONALEESA-2 and also from the data of PALOMA-1 and PALOMA-2 that the CDK4/6 inhibitor in combination with an endocrine therapy can increase progression free survival with a dramatic benefit for patients in terms of clinical benefit rate with a very low toxicity. So I am quite sure that for the future we will have less patients receiving chemotherapy.
Does this come alongside the changing field of genomic screening?
This is an important topic, I am quite sure. Precision medicine is not ready for prime time because for some diseases of course you have a target, specific target, that is decided for a drug. For breast cancer you have very few targets, one of these is the oestrogen receptor and it’s quite clear that if you combine an endocrine therapy with a CDK4/6 inhibitor you have a dramatic benefit. Another target is CRB2 and we know very well the history of pertuzumab and trastuzumab. Unfortunately for triple negative breast cancer we don’t have still no targets.
What is your interpretation of the results from the MONALEESA trial?
I believe the results are outstanding, they replicate exactly the same results of the PALOMA-2 trial. I am quite sure that there is a reporting of toxicity that is slightly more in respect to the PALOMA-2 in terms of infections, let’s say. It’s well reported in The New England. It’s quite surprising that EMA, the European Medicines Agency, decided to reject the accelerated approval for ribociclib.
Where do you see CDK4/6 moving in the future?
First of all we can wait for the abemaciclib data. Yesterday we listened about a new adjuvant trial with a dramatic effect on Ki67. I believe the future of CDK4/6 inhibitors is in the adjuvant setting. There is a post neoadjuvant setting ongoing of the German Breast Group and if the results will be positive we have the rationale to move in the adjuvant setting in ER positive breast cancer.
Do you think it could be used in first line treatment?
It’s quite a little bit different because PD1 inhibitors are more toxic and it’s quite unusual to deliver a PD1 inhibitor for one year in the adjuvant setting. It’s more useful, I believe, to deliver CDK4/6; we have many patients in the metastatic setting receiving a CDK4/6 for more than one year. I believe we will have very interesting trials in the HER2 population. We are actually running two trials, one with the dual blockade pertuzumab, trastuzumab, endocrine therapy and palbociclib, and another one with trastuzumab plus palbociclib plus endocrine therapy. So maybe also we will have effect in the HER2 population in the neoadjuvant setting.
So my conclusion is that CDK4/6 inhibitors change the landscape in ER positive metastatic breast cancer. They should be considered the first line treatment in these patients. If they are progressing you have also a study in the second line, that is the PALOMA-3, so we have also a second line. We should explore for the future, I believe, mechanisms of resistance to CDK4/6 and maybe having new trials combining CDK4/6 with other agents like PI3 kinase inhibitors.