Management of HER2 positive metastatic breast cancer treatment algorithm

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Published: 31 Jan 2023
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Prof Sandra Swain - Georgetown University Medical Center, Washington DC, USA

Prof Sandra Swain speaks to ecancer at BGICC 2023 about the management of HER2 positive metastatic breast cancer treatment algorithm.

She highlights that a number of significant advances have been made in this area over the past few decades.

Prof Swain also outlines the key findings of one of her previous studies, CLEOPATRA, which showed a 37% survival at 8 years for HER2 positive metastatic breast cancer patients.

The management of HER2 positive metastatic breast cancer is one of my favourite topics because we’ve done so well with this over the years. It’s probably taken, I don’t know, thirty, forty, fifty years to get to where we are today with it but we’ve made huge advances. It used to be that all of these patients whose tumours had HER2 positive oncogene in them basically died; they did not do well at all and especially with metastatic disease they survived a very short period of time. Now, with the CLEOPATRA study, which I published about ten years ago now, and a couple of years ago the overall survival showing that these patients do exceedingly well with trastuzumab pertuzumab and a taxane first line metastatic, we see that 37% of those patients at eight years are alive and that’s just remarkable that this has happened. 

Since then, since that study, we have another exciting drug, trastuzumab deruxtecan, which is really changing also the trajectory of the patient with HER2 positive breast cancer. The survival outcomes are absolutely phenomenal in the DESTINY trials, the DESTINY 02 and 03 trials, that are comparing… one of them compared it to TDM-1, the other one compared it to physician’s choice, both of them showed an outstanding result with T-DXd. So T-DXd, or trastuzumab deruxtecan, is now second line in the US for sure and if patients recur early it even moves into the first line. It is being tested in first line, it is being tested in the neoadjuvant setting and it is being tested post-neoadjuvant. So things are going to really change over the next two or three years, that we’re going to see that moving up much earlier on rather than having it in metastatic disease and then maybe metastatic disease will disappear; it’s already decreasing because of the effective therapies that we’ve had.

Now, the caveat to trastuzumab deruxtecan is one of the toxicities is very serious, interstitial lung disease. In one of the DESTINY studies it was 15% of patients who had this and in all the data altogether for trastuzumab deruxtecan probably 1-2% of patients actually can die from this. It seemed to be decreasing in the more current studies because it’s being recognised. So it’s incredibly important if people are using this drug to recognise and to tell the patients if there’s any symptoms of shortness of breath or anything like that they need to be evaluated immediately and usually started on steroids and the T-DXd stopped. So we’re hoping that we’re going to see a decrease in that as people are more familiar with it. But it’s very exciting because it’s really changing things; it’s also looking like it’s effective in patients who have brain metastases.

Now, the other treatment, tucatinib, which is a tyrosine kinase inhibitor, with capecitabine and trastuzumab, has shown also, and just with a recent update, really great survival benefit in patients who have active brain mets. That’s truly also remarkable. So I’m excited because the patients are doing well, they’re living long. I personally have a patient that has had brain mets now for three years and is doing fantastic – she’s actually on T-DM1 which is also very active in HER2 positive brain metastasis. So it’s very rewarding, certainly for the patients and also for the patients to know that so much research is being done and so many advances are being done.