This transcript has been edited for clarity.
Hi. It's Dr Kathy Miller from Indiana University.
RxPONDER, you will recall, was an attempt to expand the results of the use of multiplex testing — in this case, with the Oncotype DX Recurrence Score assay — to our patients with lymph node–positive disease.
Several years ago, we saw the results of the randomized TAILORx trial.
This trial enrolled women with ER-positive, node-negative disease, randomizing those with scores between 11 and 25 to chemotherapy or hormone therapy alone, and clearly showed that there was no benefit to chemotherapy in postmenopausal women.
The results in premenopausal women were a bit more challenging, with a very small improvement, particularly in those with higher-range intermediate scores. However, data really suggest that the lion's share, if not the entire benefit, of chemotherapy in that group came from the impacts of chemotherapy on the ovaries.
The RxPONDER trial took this to node-positive patients. Because many were concerned about losing the benefits of chemotherapy in this higher-risk group, patients with low and intermediate scores (that is, scores < 25) and one to three positive nodes were randomized to chemotherapy and hormone therapy or hormone therapy alone.
The results could not be more convincing.
In the postmenopausal patients, which was roughly 75% of the patients enrolled in this trial, there was absolutely no benefit to chemotherapy — not a trend, not a hint, not a suggestion. Importantly, the number of nodes didn't matter. There was no difference with one positive node or three positive nodes. For me, this means I'm comfortable expanding these results to patients who have four or five nodes. The biology speaks very clearly. Lymph nodes tell us about risk; biology drives what we can do that will impact that risk.
The results in the small group of patients who were premenopausal were a bit more nuanced and challenging. As in the TAILORx trial, only about 15% of patients enrolled in RxPONDER who were premenopausal received ovarian suppression as their form of hormone therapy.
In that very small, underpowered subset, there was no difference in outcome. The benefit in premenopausal women who were not receiving ovarian suppression was about 3%. Again, the data suggest that the vast majority, if not the entire benefit, of chemotherapy comes from the ovarian suppressive effect. To say that another way, chemotherapy in these premenopausal women is a toxic form of ovarian suppression.
I can't exclude that there is some small, separate benefit of chemotherapy, even in premenopausal women who have optimal hormone therapy with ovarian suppression, but the trial was not designed to answer that question. However, I can conclude that the benefit is very small and that chemotherapy is no longer a mandate or a firm recommendation in those patients.
This is a great day for our patients in terms of the more rational use of chemotherapy — that is, getting chemotherapy to those who need it and will benefit from it, and sparing the toxicity from those who won't benefit.
It's also a great day for us, as a community, to see the work over so many years come to fruition.
Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.
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Cite this: Kathy D. Miller. RxPONDER: Chemo 'No Longer a Mandate' for Some With Breast Cancer - Medscape - Jan 04, 2021.