By Kate O’Rourke
Postmenopausal women with early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer who receive adjuvant endocrine therapy and have an Oncotype Dx test recurrence score of 0 to 25 can safely avoid chemotherapy. This finding comes from an interim analysis of data from the multinational, phase 3 SWOG S1077 RxPONDER trial presented at the 2020 San Antonio Breast Cancer Symposium.
RxPONDER included 5,015 patients with stage 2-3 breast cancer involving one to three axillary lymph nodes and no distant metastasis who had a recurrence score of 25 or lower. Patients were assigned to receive endocrine therapy alone or endocrine therapy plus chemotherapy. The current median follow-up is 5.1 years (Abstract GS3-00).
In postmenopausal patients – who were roughly two-thirds of the study cohort — there was no difference in 5-year invasive disease-free survival (IDFS) between those who received chemotherapy and those who did not (91.6% vs. 91.9%).
“Postmenopausal women with one to three lymph nodes involved and a recurrence score of 0 to 25 can likely safely forego adjuvant chemotherapy without compromising invasive disease-free survival,” said Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, who presented the study findings. “This will save tens of thousands of women the time, expense, and potential harmful side effects that can be associated with chemotherapy infusions.”
However, in the premenopausal cohort, those who received chemotherapy had improved 5-year IDFS, compared with those who did not receive chemotherapy (94.2% vs. 89.0%; P=0.0004), as well as a 53% improvement in overall survival (P=0.032).
The researchers identified an early overall survival improvement at 5 years with the addition of chemotherapy in premenopausal women. “This absolute benefit at 5 years was 1.3% favoring chemotherapy followed by endocrine therapy versus endocrine therapy alone,” Dr. Kalinsky said.
Overall survival data is limited due to the number of events at the time of evaluation. Results were similar in premenopausal women with recurrence scores of 0-13 and those with scores of 14-25. Among premenopausal women, the receipt of ovarian suppression was more common in patients who received endocrine therapy alone than in those who also received chemotherapy (15.9% vs. 3.7%). It is unknown to what extent the chemotherapy benefit observed in the premenopausal women was due to chemotherapy-induced menopause.
Previously, an exploratory analysis from the TAILORx trial in lymph-node negative, ER-positive breast cancer showed that patients older than 50 years with an Oncotype Dx recurrence score of 25 or lower derive no benefit from chemotherapy, while those age 50 years or younger with a recurrence score 16-25 may derive benefit from chemotherapy.
“The results from RxPonder clearly show no benefit to adding chemotherapy to standard endocrine therapy in postmenopausal patients despite having positive nodes, emphasizing that node-positivity, while an important prognostic marker, is not a predictive marker of chemotherapy sensitivity,” said C. Kent Osborne, MD, founding director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston, who was not involved with the study.