Just in are the results of the SWOG S1007 RxPONDER trial, which evaluated the benefit of chemotherapy in women with early-stage, hormone receptor (HR)-positive, node-positive breast cancer. Based on the findings, many postmenopausal women may be able to safely skip adjuvant chemotherapy. However, premenopausal women may derive a benefit from it. Kevin Kalinsky, MD, MS, and colleagues presented these results at the 2020 San Antonio Breast Cancer Symposium (Abstract GS3-00).
The findings somewhat echo those of the phase III TAILORx trial, which also sought to identify subsets of patients—with node-negative disease—who fare well with endocrine therapy alone.
RxPONDER found that postmenopausal women with HR-positive, HER2-negative breast cancer with one to three positive nodes and a 21-gene recurrence score (RS) of ≤ 25 (Oncotype DX) derived no further benefit from chemotherapy added to endocrine therapy and can safely avoid adjuvant treatment with it. On the other hand, premenopausal women with the same characteristics experienced a 45% relative risk reduction in invasive disease–free survival events with the addition of chemotherapy, according to Dr. Kalinsky, Director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, Atlanta.
Kevin Kalinsky, MD, MS
“Premenopausal patients with one to three positive nodes and an RS ≤ 25 should consider adjuvant chemotherapy. The invasive disease–free survival rate improved by 5% with chemotherapy in this group,” he said.
RxPONDER aimed to determine which patients with HR-positive, HER2-negative breast cancer and one to three positive axillary lymph nodes would benefit from chemotherapy and which could safety avoid it. It is the first large, randomized trial to try to answer this question.
RxPONDER enrolled 5,015 patients with stage II/III breast cancer, one to three involved nodes, and a RS ≤ 25. Patients were assigned to receive either endocrine therapy or endocrine therapy plus standard chemotherapy. The data were stratified by RS (0–13 vs 14–25), menopausal status, and axillary dissection vs sentinel node biopsy. There were 3,350 postmenopausal and 1,665 premenopausal women included in the study.
The primary endpoint was invasive disease–free survival, defined as local, regional, or distant recurrence, any second invasive cancer, or death from any cause.
5.2% Benefit in Premenopausal Subset
At a median follow-up of 5.1 years, after 54% of the anticipated events had occurred, there was no association between chemotherapy benefit and RS values between 0–25 for the entire population (P = .30). However, a prespecified analysis did show a significant association between chemotherapy benefit and menopausal status (P = .004), triggering further analyses of menopausal subsets.
Although premenopausal women with RS 0–25 had an invasive disease–free survival benefit with the addition of chemotherapy, postmenopausal women did not. In the premenopausal subset, the absolute benefit was 5.2% at 5 years.
Five-year invasive disease–free survival rates were 91.9% for endocrine therapy plus chemotherapy vs 91.6% for endocrine therapy alone in the postmenopausal patient subset (hazard ratio [HR] = 0.97, P = .82), and 94.2% vs 89.0% in the premenopausal patient subset (HR = 0.54, P = .0004).
Although follow-up is still very limited, especially considering these patients have HR-positive disease, chemotherapy also conferred a 1.3% absolute benefit in 5-year overall survival in the premenopausal cohort: 98.6% vs 97.3% (HR = 0.47, P = .032). In contrast, in postmenopausal women, these survival rates were 96.2% and 96.1%, respectively (HR = 0.96, P = .79).
C. Kent Osborne, MD, FASCO, Founding Director of the Dan L. Duncan Comprehensive Cancer Center and the Dudley and Tina Sharp Chair for Cancer Research, Baylor College of Medicine, said the results of the study were clear, but the explanation for the findings is less so.
“The results of RxPONDER clearly show no benefit to adding chemotherapy to standard endocrine therapy in postmenopausal patients, despite their having positive nodes. This emphasizes that node positivity, while an important prognostic marker, is not a predictive marker of chemotherapy sensitivity. In premenopausal patients, a different result was obtained,” he said.
C. Kent Osborne, MD, FASCO
But Dr. Osborne questioned where this effect is actually coming from: could premenopausal women receiving chemotherapy be experiencing the benefits of ovarian suppression, which is known to improve outcomes?
“Unfortunately, we may never know,” he said. “I’m still skeptical that chemotherapy works differently in premenopausal women and I would hate for oncologists to come away with the message that all premenopausal patients fitting these criteria should get chemotherapy.”
Disclosure: Dr. Kalinsky has served in advisory or consulting roles for Eli Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Immunomedics, Merck, Seattle Genetics, and Cyclocel; his spouse owns stock in Grail, Array BioPharma, and Pfizer. Dr. Osbourne has book royalties from Wolters Kluwer, serves on the advisory board and has minor stock holdings in GeneTex, and serves on the data monitoring committees of Eli Lilly and Tolmar.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.