RxPONDER Trial in HR+ Operable Breast Cancer

Priyanka Sharma, MD: TAILORx was focused on patients with lymph node-negative disease. We’ve had data from a previous study, SWOG-8814, again, retrospective data, that suggested predictive value of a recurrence score for chemotherapy benefit in postmenopausal women with lymph node-positive disease. That was the premise for the design for SWOG-1007, also known as the RxPONDER trial. That trial aimed to evaluate the value of the Oncotype DX recurrence score in patients with lymph node-positive, hormone receptor-positive, HER2-negative breast cancer and the benefit of chemotherapy in these patients. The primary objective of SWOG-1007 was to determine the effect of chemotherapy on invasive disease-free survival [IDFS] in patients with 1 to 3 positive lymph nodes, so those with N1 disease and a recurrence score of less than 25. Another objective was to assess whether the effect of chemotherapy was dependent on the actual recurrence score value. The SWOG trial randomized patients with a recurrence score of 0 to 25 and included both pre and postmenopausal women. This randomization was stratified based on the actual recurrence score, whether it was 0 to 13 or 14 to 25, menopausal status, and the type of axillary surgery. Patients received either endocrine therapy of physicians’ choice, or chemotherapy followed by endocrine therapy.

The primary analysis for the trial was to look at the interaction of chemotherapy and continuous recurrence score for invasive disease-free survival. If this interaction was thought to be significant, it would show that the magnitude of benefit of chemotherapy was dependent on the recurrence score. If this interaction was not significant, then the trial would aim to look at whether recurrence score and chemotherapy are independently prognostic or whether chemotherapy improves IDFS in patients with a recurrence score of 0 to 25. The trial enrolled about 5000 patients and included both pre and postmenopausal patients, like I mentioned. About two-thirds of the patients were postmenopausal and one-third were premenopausal. Almost 90% of patients had 1 to 2 nodes, so a small percentage, 10%, had 3 positive nodes. About 85% to 90% of patients had low- or intermediate-grade disease. In terms of axillary surgery, about two-thirds had a full ALND [axillary lymph node dissection], and the remaining one-third, a little over a third actually, had only sentinel lymph node biopsies. The surgery reflects some of the shifts in how the axilla is managed in patients with limited nodal disease.

What the trial showed is that in the entire trial population, there wasn’t a difference in invasive disease-free survival between chemotherapy plus endocrine therapy, or endocrine therapy alone. Also, there was no interaction between chemotherapy benefit and the actual recurrence score. The chemotherapy benefit was not dependent on recurrence score. In other words, it was not any larger in higher recurrence score categories or lower in lower recurrence score categories. What it did note was that there was a significant interaction between chemotherapy benefit and menopausal status. When you look at the pre and postmenopausal women separately, the 5-year IDFS in postmenopausal women was 92% in both the endocrine therapy arm and the chemotherapy plus endocrine therapy arm. Whereas in premenopausal women, there was significant improvement in IDFS in the chemotherapy plus endocrine therapy arm compared to endocrine therapy. The absolute difference was about 5%.

These results were reported at almost 60% of the total events expected in the trial, so more events are expected. In the presentation, the study team also provided a breakdown regarding the type of IDFS events. About 70%-plus of the events in premenopausal women were either distant recurrence or locoregional events, so the majority of the events were breast cancer related. An absolute difference in distant recurrence in premenopausal women was about 3% between chemotherapy and endocrine therapy versus endocrine therapy. When they looked at subgroups, the benefit of chemotherapy in premenopausal women was seen in all subgroups that were shown, regardless of the number of positive nodes, the actual recurrence score category, age, and grade. On the forest plot, one could see that perhaps the absolute benefit of chemotherapy in premenopausal women who were ages 50 and older was a little less than those who were less than 50. This may all go back to how menopausal status was defined, and perhaps some of those women who were over the age of 50 who were categorized as premenopausal were actually postmenopausal. Based on the postmenopausal group, we wouldn’t expect this subgroup to benefit.

Transcript Edited for Clarity