Patients with operable triple negative breast cancer are sensitive to chemotherapy with anthracyclines and taxanes but in spite of that therapy a significant proportion of them will eventually relapse. So we need new approaches to avoid those relapses.
We thought that capecitabine, an oral drug with low toxicity that is not co-resistant with conventional chemotherapy, anthracyclines and taxanes, could be an interesting drug to be added in sequence to the conventional chemotherapy to avoid those relapses. So we designed a trial in 2004, so fourteen years ago, in which patients with operable triple negative breast cancer after having received chemotherapy, usually with anthracyclines and taxanes, plus or minus radiation were stratified according to institution, basal-like status defined centrally by IHC, number of axillary nodes and type of chemotherapy – anthracyclines plus or minus taxanes – and randomised one to one to oral capecitabine, eight cycles, or observation.
What did you find?
The main endpoint was disease free survival and we didn’t find a significant increase in disease free survival from a statistical point of view, although there was a trend in favour of capecitabine, there were less relapses with capecitabine than with observation. In fact, we underestimated the behaviour of the control arm, the outcome of the control arm. The control arm behaved better than expected and this is probably one of the reasons for the lack of statistical significance.
One thing very intriguing we found is that a subset of patients prospectively formed, patients with non-basal phenotype, actually get a huge benefit with anthracyclines, both in terms of disease free survival and overall survival. So we are trying to better understand what is the reason why this population get the benefit and the basal-like population, supposedly more aggressive, didn’t. It seems like capecitabine is specific for that population so we are trying to do more studies at the molecular level. We are trying to collaborate with investigators from the CREATE-X trial, another trial testing extended capecitabine after conventional chemotherapy, in order to reproduce our findings because our findings could be true or could be an artefact. We need to understand which one is true because this could be very relevant for the patients.
Were there any adverse effects?
Capecitabine is a very known drug for breast cancer oncologists because it is used in many, many patients so most doctors know how to handle capecitabine. The main side effects are hand and foot syndrome, some diarrhoea, some myelosuppression but on the other hand it doesn’t produce alopecia and other unpleasant side effects of chemotherapy. In our trial 75% of patients actually completed the eight planned courses of chemotherapy with capecitabine.
Is there anything you would like to add?
We need more studies in TNBC; we need to understand better which is the molecular situation behind that classification because probably TNBC is not a single entity but it is a miscellaneous entity. We need to learn which different subgroups are in there and we need to run specific trials, probably, in each of the subpopulations.
