Chemotherapy plus endocrine therapy improved 5-year invasive disease-free and overall survival in premenopausal women with HR–positive, HER2-negative, lymph node–positive breast cancer and a recurrence score between 0 and 25.
Menopausal status may determine clinical benefit from the addition of chemotherapy too endocrine therapy in women with hormone receptor (HR)–positive, HER2-negative, lymph node–positive breast cancer and a recurrence score between 0 and 25, according to findings from a prespecified interim analysis of the phase 3 RxPONDER trial that were presented virtually during the 2020 SABCS.
In particular, the addition of chemotherapy to endocrine therapy led to an improvement in 5-year invasive disease-free survival (iDFS) and overall survival (OS) in premenopausal but not postmenopausal women.
In premenopausal patients, the 5-year iDFS rate was 94.2% in the chemotherapy/endocrine therapy arm vs 89.0% in the endocrine-alone arm, reflecting an absolute difference of 5.2% (adjusted HR, 0.54; 95% CI, 0.38-0.76; P = .0004). In postmenopausal patients, the 5-year iDFS rate was 91.6% and 91.9%, respectively (adjusted HR, 0.97; 95% CI, 0.78-1.22; P = .82).
“Postmenopausal women with 1 to 3 positive nodes and recurrence score between 0 and 25 can likely safely forego adjuvant chemotherapy without compromising iDFS,” Kevin Kalinsky, MD, lead study author, director of the Glenn Family Breast Center and Breast Medical Oncology at Winship Cancer Institute, and acting associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, said in a press briefing.
“This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions,” Kalinsky added. “[However,] premenopausal women with positive nodes and recurrence scores between 0 and 25 likely significantly benefit from chemotherapy.”
Patients with HR–positive, HER2-negative, lymph node–positive breast cancer have an increased risk of recurrence and are typically treated with chemotherapy.
To prevent potential overtreatment or undertreatment, the 21-gene Oncotype Dx Recurrence Score is used to identify which patients with lymph node–negative, HR-positive, HER2-negative disease can omit chemotherapy.
In lymph node–negative patients, exploratory findings from the phase 3 TAILORx trial suggested that women over the age of 50 with a recurrence score of 25 or less derive no benefit from chemotherapy, whereas patients age 50 or under with a recurrence score between 16 and 25 may derive benefit from chemotherapy. However, whether these results were generalizable to the approximately 20% of patients with nonmetastatic HR-positive, HER2-negative disease and 1 to 3 positive lymph nodes in the United States had not been previously defined.
To that end, investigators launched RxPONDER, in which 5015 patients with a recurrence score between 0 and 25 were randomized to endocrine therapy alone or chemotherapy followed by endocrine therapy. Patients with a recurrence score of more than 25 were treated off study with chemotherapy followed by endocrine therapy.
Patients in the randomized portion of the trial were stratified by recurrence score (0-13 vs 14-25), menopausal status (pre vs post), and nodal surgery (axillary lymph node dissection vs sentinel lymph node biopsy).
Eligible patients included females 18 years of age or older with at least 1% estrogen receptor and/or progesterone receptor expression, HER2 negativity, 1 to 3 positive lymph nodes, recurrence scores of 25 or less without distant metastases, and an ability to receive taxane and/or anthracycline-based chemotherapy.
iDFS, defined as local, regional, distant recurrence, any second invasive cancer, or death due to any cause, served as the primary end point of the study. OS served as the secondary end point.
Additional results demonstrated that the iDFS benefit also translated into an OS benefit in premenopausal patients. In this population, the 5-year OS rate was 98.6% with chemotherapy/endocrine therapy vs 97.3% with endocrine therapy alone, reflecting an absolute improvement of 1.3% (adjusted HR, 0.47; 95% CI, 0.24-0.94; P = .032). However, in postmenopausal women, the 5-year OS rate was 96.2% and 96.1%, respectively (adjusted HR, 0.96; 95% CI, 0.70-1.31; P = .79).
Providing additional perspective during the press briefing, SABCS co-director, C. Kent Osborne, MD, founding director of the Dun L. Duncan Comprehensive Cancer Center and Dudley and Tina Sharp Chair for Cancer Research at Baylor College of Medicine, added, “The results 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.”
“In premenopausal patients, a different result was obtained. Is the difference in outcome in this subset due to the endocrine effects of chemotherapy? Unfortunately, we may never know the answer to this question,” Osborne concluded.
Kalinsky K, Barlow WE, Meric-Bernstam F, et al. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy +/-chemotherapy in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative breast cancer with recurrence score of 25 of less: SWOG S1007 (RxPONDER). Presented at: 2020 SABCS. December 8-12; virtual. Abstract GS1-00.