Our study focusses on the clinical value of the HER2DX genomic test. This is a newly developed gene expression-based assay that includes 27 genes that track four main biological features of HER2 positive breast cancer – the immune component, the proliferation of tumour cells, the luminal differentiation, as well as the HER2 expression itself. This genomic test integrates all these four data types into a final score, a score meant to predict prognosis in early stage HER2 positive disease and a score meant to predict the probability of achieving a pathological complete response after neoadjuvant trastuzumab-based chemotherapy. At San Antonio we have presented several studies looking at this assay in particular clinical trials.
What were your findings?
On the one hand, HER2DX was evaluated in what we call clinically low risk disease and this was two validations of HER2DX in two very important studies that were previously reported. One is the APT phase II clinical trial that led to the approval of paclitaxel and one year of trastuzumab in the adjuvant setting in small tumours node negative and the other one was a validation in the ATEMPT trial, a study meant to evaluate adjuvant T-DM1, 17 cycles, versus a TH regimen of the APT trial. So we’re talking about a retrospective validation in these two trials of the HER2DX risk score, showing that in both trials the HER2DX risk score is able to predict prognosis, despite this being a patient population with very low risk overall.
How does this tool affect clinical practice?
On the one hand we have these clinically low risk disease patients where we are de-escalating treatment using a single taxane and one year of trastuzumab for many of these patients. But there are still doubts who should receive a de-escalated systemic treatment regimen versus the standard therapy which would be multi-agent chemotherapy and one year of trastuzumab. Now that the HER2DX assay is able to provide prognosis in this setting it may allow us to better decide who needs the de-escalation strategy versus who needs the standard multi-agent chemotherapy and one year of trastuzumab.
This is one setting. The other setting is in the neoadjuvant context in stage 2 or stage 3 disease. Today we treat these patients mostly with neoadjuvant trastuzumab-based chemotherapy; the question is if we can predict different responses, different probabilities of achieving a pCR and if we can predict the response to pertuzumab, the second anti-HER2 agent that we include, or we add, on top of chemotherapy and trastuzumab.
At San Antonio we have presented two independent validations of the HER2DX pCR score in the DAPHNe phase II clinical trial where all patients received a taxane, paclitaxel, trastuzumab and pertuzumab for three months and also the GOM series from Spain where all patients received docetaxel and carboplatin and some patients received trastuzumab and some patients received trastuzumab pertuzumab.
Across these two trials with more than 200 patients, we showed that the HER2DX pCR score predicts pCR independently of all the known clinical pathological variables, including intrinsic subtype. Also we showed that patients with HER2DX pCR high scores are the ones who benefit the most from the addition of pertuzumab to chemotherapy and trastuzumab.
So now we have validated, again, in the context of pertuzumab the pCR score allowing in the future a better tailoring of who needs more escalated therapy with multi-agent chemotherapy and dual blockade and who needs just a taxane and dual blockade.