Metastatic breast cancer is a very large field and I gave an overview of the recent advances in this domain. The biggest advances are in the luminal breast cancers, the ER positive, HER2 negative breast cancers, where we have the introduction of the CDK4/6 inhibitors. There are three molecules, palbociclib, ribociclib and abemaciclib, and all three have shown in the general population to extend the progression free survival from about 14 months to about 24 months. So it’s a huge improvement in disease control with very little additional toxicity.
I reviewed the age specific data for these three molecules and it seems that both the efficacy and the toxicity of these new molecules do not seem to differ much between the older and the younger population in the trials. Because we know that only fitter older patients go into trials. We also need data on the use of these molecules in frail patients and we don’t have this data yet. But so far it looks encouraging and I think these drugs will also be used a lot in older persons.
There are data with these new molecules in first line combined with an aromatase inhibitor and in second line combined with fulvestrant. The big question is which are the patients where you can first give an aromatase inhibitor alone which is much cheaper and easier and then you use your CDK4/6 inhibitor as second line therapy. But we are looking for biomarkers and for older individuals also it’s much easier to take one tablet of aromatase inhibitor instead of taking these new molecules that require frequent blood sampling and frequent visits to the hospital. So that’s an area of further research for the future.
That’s the biggest improvement in luminal breast cancer. For the HER2 positive breast cancer subtype there are also some new data upcoming. The standard first line therapy for that setting is taxane/trastuzumab/pertuzumab but a taxane is not so easy in frail older patients and we are looking to de-escalate the regimens and trying to avoid the taxane. There are two recent trials that have reported partially their data. The first is the PERTAIN study where they looked at giving an aromatase inhibitor with trastuzumab/pertuzumab but the study was a complex study and the conclusions were not so clear on whether you can avoid the taxane or not. A second study is an AORTC study that I coordinated where we completely omitted the taxane and we gave only pertuzumab/trastuzumab. It was a two-arm study, trastuzumab/pertuzumab alone or combined with metronomic chemotherapy, oral low dose chemo. We have this paper accepted in Lancet Oncology but it will only be published in a few weeks so I cannot disclose the results yet but they are interesting. I’m sure that the readers will be able to find the publication in Lancet Oncology soon.
Concerning the triple negative, the third subtype of breast cancer, this is a more rare subtype in older persons and we have not seen so much improvement in that area for the older person. There is a lot to do about immune therapy in that subset but it’s not ready for the clinic at this moment.