The best sequence of anti-HER2 therapy in metastatic breast cancer

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Published: 29 Jan 2018
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Dr Javier Cortes - Vall d’Hebron University Hospital, Barcelona, Spain

Dr Cortes speaks with ecancer at the 10th BGICC in Cairo about treatment sequencing for patients with HER2 positive breast cancer.

He details treatment options assessed in recent trials, including TDM1, trastuzumab emtansine and lapatinib, and control of brain metastasis.

Dr Cortes also gives his position from the conference debate on the suitability of combined adjuvant anti-HER2 therapy, arguing for.


Basically the presentation is about how to optimise the sequence in HER2 positive metastatic breast cancer. It's quite easy to see that we have a clear sequence to treat our patients when they have HER2 positive metastatic breast cancer. The role of pertuzumab and trastuzumab-based therapy in the first line setting is very well established and maybe the key point is how to treat our patients afterwards. We have great data with TDM1 showing a clear advantage when it has been compared with lapatinib and cape. But also we have there's a trial which compared TDM1 versus physicians choice, both trials were absolutely positive for the primary endpoints, progression free survival and overall survival, and, from my point of view, we have to understand that the earlier the better. That is why TDM1, or Kadcyla, should be used as soon as possible in those patients who are resistant or refractory to trastuzumab and taxane based therapy. That's why, in my opinion and this is what we have discussed, is the first line setting should be pertuzumab and trastuzumab based therapy followed by TDM1.

Unfortunately not all patients are treated the same, of course there are many issues to be considered. But again, if possible, this sequence is quite clear or should be quite clear for treating the majority of our patients. Of course not for all of them but for the great, great majority, I would say maybe for 90-95% of them at least, this is a very reasonable sequence.

I have been talking also about brain metastasis from HER2 positive breast cancer and here, and again this is my opinion, we should not change the way we treat our patients. Pertuzumab therapy should be also the standard of care in the first line setting followed by TDM1. So in my opinion brain metastasis should not change the sequence of treating our patients.

Does this impact on care afterwards?

You're right, when we are facing patients with brain metastasis from breast cancer some of our colleagues believe that other sequences could be even a better approach, something like lapatinib plus something. I think it's a good approach as well but we should not forget the data we have from the EMILIA in which those patients who had non-progressive brain metastasis had an overall survival benefit if they were treated with TDM1 compared with lapatinib based therapy .So, again, that's why I think that TDM1 is also the preferable option in the second line setting if the patients have brain metastasis.

Are you aware of any ongoing trials that are worth noting?

It would be great to have some trials for brain metastasis from breast cancer which, to the best of my knowledge, we do not have that many. We have some trials with tucatinib, which is a new tyrosine kinase inhibitor, and also we have some trials with a new chemotherapeutic compound called irinotecan for patients with stable non-progressive brain metastasis.
We also had a great debate with Hope Rugo, trying to discuss which is the optimal treatment for early breast cancer. So, should you combine trastuzumab and pertuzumab for HER2 positive early breast cancer patients or can we go for Herceptin only? This is a great debate, everything is still not as easy as in the metastatic disease but, in my opinion, at least for patients with ER negative and/or node positive tumours trastuzumab and pertuzumab should be clearly discussed and clearly at least offered. The reason is very simple - the hazard ratio is below 0.80, in the range of 0.77 or 0.76, the absolute improvement at four years is in the range of 3% for this group of patients and I'm pretty sure that with a long-term follow up we'll see higher absolute benefits. So, again, for this group of patients, ER negative and/or node positive, in my opinion pertuzumab and trastuzumab should be considered for the majority of our patients.