RxPONDER: sparing chemotherapy in post-menopausal patients with node-positive early-stage breast cancer
The de-escalation and treatment personalization of patients with early breast cancer has advanced in recent years, with studies such as TAILORx (NCT00310180) demonstrating adjuvant endocrine therapy alone is sufficient for most patients with intermediate-risk breast cancer.1 At the San Antonio Breast Cancer Symposium 2020 (SABCS 2020), the results of the SWOG S1007 RxPONDER trial (NCT01272037) were presented, providing more evidence for the de-escalation of therapy in patients with node-positive, endocrine responsive breast cancer.
RxPONDER is an ongoing randomized Phase III study analyzing the benefit of adjuvant chemotherapy in women with early-stage, hormone-receptor (HR)-positive, node-positive breast cancer. In this study, 5,015 women with HR+, HER2- breast cancer with 1–3 involved nodes and a recurrence score of ≤5 were randomized 1:1 to receive endocrine therapy or chemoendocrine therapy. The primary objective of the study was to determine the effect of chemotherapy on invasive disease-free survival (IDFS) and whether this effect was dependent on the recurrence score.
With a median follow-up of 5.1 years, there was no significant association between chemotherapy benefit and continuous recurrence score for the entire population, p=0.30. Pre-menopausal women with a recurrence score of ≤25 had an IDFS benefit with the addition of chemotherapy, with an early indication of an overall survival improvement; however, this was not observed in the post-menopausal cohort. Furthermore, the 5-year IDFS was 91.9% in post-menopausal patients treated with chemoendocrine therapy, in comparison to 91.6% in patients treated with endocrine therapy alone.
Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute, Boston, MA, discusses the implications of the results of this practice-changing study…
“The study showed that in post-menopausal women, there was no benefit to chemotherapy if your recurrent score was under 25. This is very practice-changing because it tells us now that we should be sending genomic assays in our post-menopausal patients with up to three positive nodes. Again, if their score comes back under 25 with one to three positive nodes, there’s no indication for chemotherapy”
Dr Tolaney also highlights the potential impact of ovarian suppression on the findings seen in premenopausal patients…
“In the premenopausal patients, there did seem to be benefit from chemotherapy. There was an absolute benefit of 5% in terms of invasive disease-free survival. There was also a survival benefit of about 1%. I think this draws a lot of questions because the majority of people in this trial did not get ovarian suppression. We do wonder if the chemotherapy in these young patients is causing suppression of ovarian function that is leading to this additional benefit or is it really the chemotherapy that’s killing cancer cells and having benefit?”
The results of RxPONDER demonstrate a significant differential treatment effect of chemotherapy benefit based on recurrence score for pre-menopausal versus post-menopausal patients, with the current data suggesting adjuvant therapy can be de-escalated to endocrine therapy alone in post-menopausal women with a recurrence score of ≤25 and 1–3 involved lymph nodes.
- Sparano J, Gray R, Makower D, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. New England Journal of Medicine. 2018;379(2):111–121.
Written by Solyana Yohannes