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SABCS 2021 | RxPONDER: is it all OFS?

Michael Gnant, MD, Medical University of Vienna, Vienna, Austria, provides a summary of a debate held during the San Antonio Breast Cancer Symposium looking at the results of the RxPONDER study (NCT01272037), which evaluated whether chemotherapy could be spared in women with node-positive early-stage breast cancer based on OncoType Dx ® score, and whether the results are a response to ovarian function suppression (OFS). This interview took place at the San Antonio Breast Cancer Symposium 2021 in San Antonio.

Transcript (edited for clarity)

I think that’s one of the crunch questions that came out of very recent trial results. In the RxPONDER trial, the specific subgroup of patients at intermediate risk was a recurrence score between 11 and 25. In the post-menopause, did not show any difference or benefit for chemotherapy. In the premenopausal setting there was a difference, approximately 5% chemotherapy benefit in terms of disease free survival...

I think that’s one of the crunch questions that came out of very recent trial results. In the RxPONDER trial, the specific subgroup of patients at intermediate risk was a recurrence score between 11 and 25. In the post-menopause, did not show any difference or benefit for chemotherapy. In the premenopausal setting there was a difference, approximately 5% chemotherapy benefit in terms of disease free survival.

When you look at the more relevant distant disease free survival, that means, keeping metastasis away, then the difference is 2.8%, which is almost identical to what was shown both in the TAILORx trial as well as in the Mandic trial. So, we can say in terms of benefit of distant disease free survival, we see about a two to 3% difference favoring chemotherapy. However, what is unknown is whether chemotherapy actually acts as cytotoxic, as we used to believe, or whether it’s a side effect of ovarian function suppression.

And obviously my task in today’s debate is to argue that most of it, if not all, is ovarian function suppression. I think there’s very good arguments for that. The old ovarian function suppression trials, based on, from nowadays perspective, suboptimal treatment combinations, actually show the benefit in the magnitude of 10, 15%. And there are, in fact, some head-to-head trials, particularly an excellent trial by the IBCSG, which, at 10 years, for the addition of anthracycline containing chemotherapy, did not show any difference in premenopausal patients.

Furthermore, one would believe that chemotherapy is particularly important for the very young patients. In fact, the opposite is true. When you look at all these trials, you see that the chemotherapy benefit comes from those age 45 to 50, where it is relatively easy to achieve ovarian function suppression. Below the age of 35, where most of our patients get chemotherapy, chemotherapy does not yield amenorrhea in a large proportion of patients, and the data demonstrate that that means that it’s not particularly working in that subgroup.

So, I think, taking all these things together, it’s fair to say that for the vast majority of patients, everybody at low risk anyway, but also for patients at intermediate risk, the addition of chemotherapy to an optimized endocrine intervention that should contain ovarian function suppression is not helpful. And chemotherapy, as I put it, is just a graceless method of achieving ovarian function suppression.

Yes, there are these patients at highest risk who benefit from chemotherapy, but I think other than in the past when almost everybody based on a young age received adjuvant chemotherapy, in the future we will confine this side effect rich treatment to those at highest risk, and fortunately these are only a small proportion of patients.

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