You are conducting, have conducted, a study of neoadjuvant therapy in triple negative breast cancer. Can you tell me what was the big topic you wanted to get an answer to?
The GeparSixto study actually was not only in triple negative breast cancer, it was also in HER2 positive breast cancer as in both subtypes the role of carboplatin is being investigated and discussed. So we added carboplatin given on a weekly basis for 18 weeks to a taxane anthracycline based chemotherapy and the triple negative patients additionally got bevacizumab in both treatment arms.
Now, that’s before surgery and quite an aggressive regimen.
It’s a very intense regimen which we believe is the right approach, especially for triple negative disease where you really have to touch the tumour right from the beginning as there the decision on the prognosis finally is being taken.
And it’s quite a big group, what happened?
What we already published in the past is that carboplatin increased dramatically the pathologic complete response but only in the triple negative patients, not in the HER2 positive patients. Now we presented three years’ survival data on these patients and could see that also disease free survival was significantly improved when carboplatin was added in but again only in the triple negative patients.
How big was the disease free survival improvement when you add in the carboplatin?
The hazard ratio was 0.56 which is quite high and that is the reason why the trial that is small, it was a randomised phase II with 315 triple negative cancers, why these results are significant, because of this high hazard ratio.
Do you think this is practice changing then?
Well, I concluded my presentation saying it supports the use because there is already quite some use of carboplatin in these patients. It’s mainly used in patients with BRCA mutation but what we also presented is that the carboplatin effect, in our trial at least, was more in the BRCA non-mutant patients whereas we believe that there is maybe a ceiling effect in the mutant patients, they already got doxorubicin as another DNA damaging agent so that carboplatin did not add there anymore. Whereas in the non-mutant, there carboplatin helped.
Can you run me through, then, what you think doctors would be doing if these results are all proven and taken note off?
The way how we are thinking about our data is that if I have a patient with triple negative disease with certain risk factors, additional risk factors – younger age, higher tumour volume, very high Ki-67 proliferation, then I would discuss with her the use of carboplatin because we have this data now. On the other hand, we know that it’s inducing additional toxicity so the risk and benefit have to be weighed. As it’s only a phase II and it’s only a subgroup and it’s only the secondary endpoint of the trial, we have to be cautious and therefore this has to be discussed with the patient. But it’s an additional option for high risk triple negative breast cancer.
What’s the optimum duration, then, of the neoadjuvant therapy?
That’s a good question. The other trial that was presented here at the meeting, the CRGB-4603, they also added carboplatin but only together with twelve cycles of paclitaxel and then the AC part was without carboplatin. They showed a quite comparable improvement in pCR rates but they couldn’t see the disease free survival effect actually. We are now struggling a bit why this trial is so different and one of the reasons might be they used carboplatin every three weeks and we used it weekly and actually we used it for 18 weeks in total and they gave it only for 12 weeks. So scheduling might play a role in here. Another reason might be that in the US much more patients are getting additional chemotherapy after surgery so maybe the control arm which was less active had more use of other chemo drugs and therefore they couldn’t see the survival difference which we saw because in Germany almost nobody gets additional chemotherapy after surgery.
OK, so it’s still a contentious issue to some extent. What would you say are the clinical messages that are beginning to emerge from this?
As I said, if I have a patient where I think high risk triple negative breast cancer I will discuss with her to give carboplatin in combination, giving it on a weekly basis together with the taxane and then followed by regular anthracycline and cyclophosphamide, for example.
And the toxicities?
If it’s only the taxane combined with carboplatin on a weekly basis this is quite well tolerated. The GeparSixto regimen I would not use currently outside of a clinical trial because it’s special, it’s specific, the bev is not available. So I would try to merge the findings of the American and our trial and make a mixture out of it with regard to the regimen.
But to sum up it looks as if neoadjuvant therapy can improve and there’s some quite big steps forward could be made.
Yes, I believe so. We were very much surprised to see this very strong effect in survival and it’s very much comparable, actually, to trastuzumab at these early days when the NOAH study was presented which also had a quite comparable improvement in pCR rate. It also had quite similar improved disease free survival like GeparSixto but in the HER2 positive field and then it was confirmed by the large adjuvant trastuzumab study. So maybe we are lucky and have the same success here.
