Post-Conference Perspectives: RxPONDER, SABCS 2020 - Episode 3

HR+ Breast Cancer: Practical Implications of RxPONDER


The practice-changing results and implications from the RxPONDER trial for early-stage HR+ breast cancer is discussed.

Lajos Pusztai, MD, PhD: More recently, we presented the results of the RxPONDER trial. The study was designed as a complementary trial to the TAILORx. Remember, TAILORx asked the question about the value of adjuvant chemotherapy in lymph node-negative, ER-positive patients with a recurrence score of 11 to 25. TAILORx asked a similar question for women with 1 to 3 positive lymph nodes, classified as stage II breast cancer. The study also asked an additional question related to whether the recurrence score itself has a chemotherapy sensitivity prediction value. That is, as the recurrence score increases, the relative benefit from chemotherapy would increase. It’s important to understand the difference between absolute and relative benefit from a particular treatment. The absolute benefit is the percentage improvement in patients who avoid a particular event. The percentage improvement increases as the risk increases. So, if you have a 5% risk of recurrence, you cannot possibly have a 10% absolute improvement in recurrence because the absolute risk is already smaller than that: it’s just 5%. The relative risk shows the relative improvement if a marker interacts with the treatment in a statistical sense. That would imply that as the marker increases, its relative benefit increases. So, instead of having a relative 5% improvement in the outcome, you get 10%, 20%, 30% improvement as the marker increases. That was an important goal of TAILORx, to test this relationship between chemotherapy sensitivity and the recurrence score. Of course, it also tested the question of whether chemotherapy improves the survival—the invasive disease-free survival or distant recurrence-free survival—of women with 1 to 3 positive nodes, with a recurrence score of less than 25. We included patients with recurrence scores of less than 11 to test the relationship between recurrence score value and chemotherapy sensitivity.

Priyanka Sharma, MD: One of the things in the trial in terms of the standard endocrine therapy the patients received that perhaps may not completely parallel or match what we do in practice today, is the use of ovarian function suppression. A small fraction of women received ovarian function suppression in this study, as reported at 6-month follow-up. Those numbers might change as the trial reports on use of ovarian function suppression at 12 or 18 months, especially in women who have received third-generation chemotherapy. Only about 15% or so of women received ovarian function suppression in the endocrine therapy arm and this number was less than 5% in the chemotherapy arm. Based on the SOFT and TEXT trials, our use of ovarian function suppression in women with high-risk disease, especially the ones who receive chemotherapy in clinical practice, has increased compared to what it was when the trial enrolled patients in SWOG-1007.

Lajos Pusztai, MD, PhD: The data was released at the San Antonio Breast Cancer Symposium last year, in 2020. The result was released prematurely since it’s not the final analysis. It was the third interim analysis. The data safety monitoring committee recommended that we publish the results. The role of the data safety monitoring committee is to determine, at predetermined points, whether a study continues to be safe. It also has resulted in a practice-changing result that the public should be aware of. The data safety monitoring committee at the third interim analysis, which was preplanned by the trial statistics, realized that there is a very significant interaction between chemotherapy benefit and menopausal status. Premenopausal women had a very significant improvement in their invasive disease-free and distant recurrence-free survival from chemotherapy, across the entire range of recurrence score values. The two-thirds of the patients in the trial who were postmenopausal didn’t benefit at all. In fact, there was a slight hint that the chemotherapy may be detrimental. The data safety monitoring committee felt that the trial actually answered its question, and the information could potentially save some younger women’s lives. It could also avoid, for many older women, the unnecessary burden and toxicity of chemotherapy. That was the reason the trial results were announced.

Transcript Edited for Clarity