APHINITY: Adding pertuzumab to trastuzumab plus chemotherapy in patients with operable HER2-positive early breast cancer
Prof Martine Piccart - Université Libre de Bruxelles, Brussels, Belgium
We are very pleased about the six year results of the APHINITY trial. If you remember well, the first primary analysis of this trial happened 2½ years ago. The follow-up at that time was 45 months. There was a statistically significant improvement in invasive disease free survival favouring the arm with pertuzumab added to chemotherapy and trastuzumab but the magnitude of benefit was very modest. Now at six years the benefit of pertuzumab is strengthened in the node positive population where we see now a 4.5% absolute benefit at six years. This benefit is to be balanced against potential harm but the good news there are that we have not seen new cardiac safety issues. So what needs to be remembered is that prescribing pertuzumab in addition to adjuvant chemotherapy and trastuzumab, and, by the way, the chemotherapy was mostly anthracycline based, is associated with a small risk of severe cardiac toxicity below 1%.
The other very important observation we made with this longer follow-up is that the benefit of pertuzumab is now independent from hormone receptor status. At the first analysis we had the impression that the treatment effect was confined to women with hormone receptor negative disease. This is no longer the case and we explained this by the fact that in hormone receptor positive disease the curves, we know that, diverge much later, the events accumulate more slowly over time and that’s why now we can see this benefit independently from hormone receptor status.
This is another step forwards towards the complete eradication of this disease in the next few years because if you look at the overall survival outcomes in APHINITY we have survival rates of 94% and we know that this disease is aggressive. So this is absolutely remarkable. By the way, we don’t see yet a statistically significant improvement in overall survival with the addition of pertuzumab but we know that this analysis is still quite immature and we will continue to follow our patients.
The important message around the world is that for high risk women with HER2 positive breast cancer it becomes indicated to think of adding pertuzumab to trastuzumab and chemotherapy. What we hope with our future research is to be able to find biomarkers of pertuzumab benefit beyond just nodal positivity. We are currently working on a step analysis for this trial. That means that we are going to build a kind of composite score that takes into account not only the nodes but the tumour size, the age, hormone receptors, infiltration by lymphocytes of the tumour which is known to be prognostic and potentially predictive even, and then the number of copies of the HER2 gene. By incorporating all these variables we will come up with a risk score and then we can see for each risk if the two treatments, the curves pertaining to the two treatments, the standard treatment and the new treatment, if they are diverging, yes or no. So my hope is really that we will be more clever with this analysis in identifying patients who really benefit from dual HER2 blockade and chemotherapy.
