Endocrine therapy plus trastuzumab and pertuzumab shows excellent survival outcomes in HR and HER2 positive early BC
Dr Oleg Gluz - Evangeliches Krankenhaus Bethesda Klinik, Mönchengladbach, Germany
We have looked at 207 patients with early breast cancer and hormone receptor positive, HER2 positive disease, and we have looked at the neoadjuvant treatment. As you know, the basis for all the discussions today that the standard treatment in these patients consists of 18-24 weeks of polychemotherapy in combination with anti-HER2 treatment. We have looked at the comparison of two different de-escalated treatments. To start with, endocrine treatment alone plus double blockade against HER2-receptor, this by pertuzumab and trastuzumab, or with de-escalated chemotherapy by twelve weeks of paclitaxel weekly combined with pertuzumab and trastuzumab. After this period of 12 weeks, surgery was performed, but it was also allowed to perform the core biopsy to confirm the [??] of pathological complete response and to continue standard treatment in the neoadjuvant way.
We have published a couple of years ago the first results from the trial which looked at the comparison of pathological complete response after de-escalated treatment. We have observed, without chemotherapy, just with endocrine therapy alone plus double anti-HER2 blockade, pathological complete response was achieved in about one quarter of all patients, 27%. If you do de-escalated chemotherapy, only 12 weeks, you achieve pCR of about 57% without polychemotherapy, so by shorter duration of chemotherapy. But we have observed very clearly higher pCR in these patients.
After the surgery, all patients were treated by chemotherapy if they didn’t have pCR, or it was recommended to do in this way, and all patients were treated by trastuzumab and pertuzumab for one year, so it was a real strong anti-HER2 treatment in these patients. Now we have looked on the survival results from the trial, and they have observed excellent survival in both groups, irrespective of if chemotherapy was done or not. This is something very interesting for the clinical practice, because you know we have started with de-escalated treatment in both cases, and about one third of all patients in the endocrine arm were never treated by chemotherapy, and about 60% of patients in the chemotherapy arm were treated only by de-escalated treatment, but we have observed excellent survival results in both groups.
What sort of toxicities were found?
For this neoadjuvant treatment, we have clearly observed that the combination of endocrine treatment without chemotherapy plus pertuzumab and trastuzumab was associated with less adverse events compared to the chemotherapy. To be honest, the monochemotherapy by paclitaxel weekly given for only 12 weeks is not so toxic compared to the polychemotherapy. So at the end of the day we have observed excellent safety results in both arms, absolutely clearly, a better safety profile for endocrine treatment, quality of life maintained in the endocrine arm, and it was decreased in the chemotherapy arm, as expected. So, for both arms, there are several arguments to be done in the clinical routine in future, because we have in both situations very effective treatment with a very safe safety profile.
What impact could these findings have?
Now, there are several prospective ongoing trials worldwide, in Spain for example, or in the US. The CompassHER2 trial or PHERGain II trial in Spain, which looks on shorter duration of chemotherapy, or, for example, omission of chemotherapy in selected cases by giving double blockade alone, anti-HER2 blockade, in combination with endocrine treatment alone. For these larger prospective trials these survival results are very important. Because for now we show for the first time that starting with de-escalated treatment is not associated with a worse outcome compared to starting with chemotherapy. It’s a very important point for many patients.
For now it’s absolutely clear. I would not say everybody could be treated by endocrine treatment plus double blockade and by chemotherapy only in the case of no pCR, because for this conclusion the study is too small. But I think the study provides significant evidence for the use of de-escalated chemotherapy, for example 12 weeks of paclitaxel if you achieve your pathological complete response, at least in patients with not so locally advanced tumours. We are not speaking about patients with 10 positive lymph nodes or tumour size over 7cm, but a majority of our patients are in between, between higher-risk and lower-risk disease. In all our classical patients, it’s 2.2cm and node-negative, and I think for these patients this regimen with paclitaxel weekly for 12 weeks and double blockade seems to be a very good compromise between efficacy, safety, and safety profile.
