You’re looking at T-DM1, this is a conjugate, a special way of fighting breast cancer cells. What were you doing in this study that you’ve been looking at that you’re quoting here? What was the big issue that you were trying to investigate in patients who have been heavily pre-treated with all sorts of things already?
T-DM1 is an antibody drug conjugate composed of trastuzumab stably linked to DM1 which is a cytotoxic microtubule inhibitor. T-DM1 is already approved based on the EMILIA study which showed increased progression free survival and overall survival in second line HER2 positive metastatic breast cancer. The goal of the TH3RESA study is to investigate T-DM1 in a more advanced population. So in TH3RESA patients were randomised 2 to 1 to T-DM1 or a treatment of physician’s choice. After a follow-up of 30 months median overall survival increased by 6.9 months.
Let me ask you a little bit about the physician’s choice because what would that have been?
The treatment of physician’s choice consisted in 80% of cases of trastuzumab-containing combinations, mostly combinations of chemotherapy with trastuzumab but also trastuzumab plus hormone therapy or lapatinib.
So these patients had already had plenty of anti-HER2 therapy because they’re HER2 positive, nevertheless that’s more or less all they could get would be something like trastuzumab afterwards.
Yes, it’s a different story, the use of trastuzumab beyond progression. There are several older studies and data that suggest that if you continue to block the HER2 that at least you slow down the progression.
Now, you gave me some figures there, could you give me the full data on what you got in terms of improvements in progression free survival and overall survival?
In the TH3RESA study progression free survival increased from three to six months with T-DM1 and overall survival increased from 15.8 to 22.7 months.
That is a big increase.
Yes, it’s a 6.9 month increase in overall survival.
I can ask was there a downside but I think almost whatever you say will be balanced by the upside. But what about toxicity?
Toxicity in the TH3RESA study was quite similar to what was reported previously. T-DM1 has a favourable safety profile; we see slightly more thrombocytopenia but we see less neutropenia, less febrile neutropenia, less diarrhoea, less nausea, less vomiting. So in general T-DM1 is a quite well tolerated drug.
And this trial is still continuing, patients are still on trial. What’s your longest lived patient so far?
Well at the cut-off date in February 2015 still about a quarter of patients were in the study. But it’s what we see with HER2 positive disease, some patients can live for years with anti-HER2 therapy.
What do you make of these findings clinically?
The TH3RESA study mainly confirms the use of T-DM1 in metastatic HER2 positive breast cancer in patients who were treated already with trastuzumab and a taxane. So we have in this setting now two very positive trials, the EMILIA study in second line and the TH3RESA study in later lines, that show progression free survival benefit but also overall survival benefit with generally less toxicity. This is unusual because in oncology we often see some increase in progression free survival at the cost of increased toxicity but this is not the case here.
What are your recommendations to doctors treating patients who are heavily pre-treated also with previous anti-HER2 therapy now then?
I can only confirm the NCCN guidelines that state that T-DM1 is the preferred regimen in HER2 positive metastatic breast cancer that was treated with taxane and trastuzumab.
Do you think there’s a case now for using T-DM1 earlier in the disease?
This study has been performed, it’s the MARIANNE study, and it was presented but in that study T-DM1 was not superior to a taxane plus trastuzumab or to T-DM1 plus pertuzumab, it was a three arm study. So at this moment we should not use T-DM1 in first line. There is a well-established first line therapy for HER2 positive metastatic breast cancer, being taxane, trastuzumab and pertuzumab. This is the first line at present but if patients fail on that therapy T-DM1 is the preferred regimen.
