Medicine Matters oncology

So RxPONDER was a study in which we randomized patients with hormone receptor positive HER2-negative breast cancer who had one to three lymph nodes involved without distant metastasis, to chemotherapy followed by endocrine therapy versus endocrine therapy alone. And at San Antonio this year, we're reporting the first results at interim analysis. And the reason that these are being reported now is because we're seeing a differential effect on invasive disease free survival per menopausal status.

So the patients who were postmenopausal, those lines fully overlap, meaning that there was no benefit with the addition of chemotherapy amongst those patients with a hazard ratio of 0.97. But if you look in the premenopausal group, you know, there was a five year invasive disease free survival benefits of a little over 5%, favoring those patients who received chemotherapy, who were randomized to chemotherapy followed by endocrine therapy versus endocrine therapy alone. The other really notable finding is that we're starting to see an overall survival benefit specifically in premenopausal patients with the addition of chemotherapy, leading to a five-year absolute improvement of about 1.3%.

So for patients who are postmenopausal, you know, I think that this is a practice changing trial, you know, for both groups. But for the implications for patients who are postmenopausal is that, you know, we've been utilizing the recurrence score, the 21-gene recurrence score to determine utilization of chemotherapy for patients with node-negative results. And we didn't know in patients who had a higher absolute risk of recurrence with one to three nodes involved, whether the same would hold true.

And we are clearly seeing, at this time, that there's no benefit for chemotherapy in this population with recurrence score of 25 or less. And the implication of this is that there will be thousands of patients who will be spared the cost, the toxicity, all the other associated issues with getting chemotherapy, right? There was no added benefit.

And when we're talking to our patients who are premenopausal, this gives us a better sense of, well, you know, for you, when this is a one-on-one conversation, that really there may be this benefit for adding in chemotherapy. And not just for invasive disease free survival, but given the information we have now, for overall survival. And now that we have these data, we're able to comment, you know, specifically when we're talking to patients, in a much more assured way of what the potential benefit of chemotherapy really is in the modern era with taxane and or anthrocycline-based chemotherapy.

These data, in some way, were demonstrated in patients in TAILORx, where they also saw, in exploratory analysis, this difference based upon age and who benefited from chemotherapy and who didn't. And you know, part of it is that, you know, in the post menopausal population, there were some events that were unrelated to specifically breast cancer, you know, such as dying from other causes, et cetera. But still, when you look at specifically breast cancer related events, numerically, there was no difference.

And the same doesn't hold true for premenopausal women. And you know, that's the question. And you know, clearly, cessation of menses is a contributing factor. Whether it's the only factor is not clear, and that's not something that this study was powered to look at.

We did collect, at various follow up time periods, whether or not patients were menstruating or not, and we will, in the future, report on various landmarked analysis. But this will be an exploratory analysis. And then the question, as a community, that we should think about is whether we, in this population, should think about prospectively analyzing this.