Bhuvaneswari Ramaswamy, MD, MRCP
Professor and Section Chief- Breast Medical Oncology
The Ohio State University Comprehensive Cancer Center
First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder)
San Antonio Breast Cancer Symposium. 2020 Dec 8-11. Virtual: Abstract GS3-00.
Can we forgo chemotherapy in select node-positive hormone receptor positive, HER2 negative breast cancer patients?
Title: RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer: First results from 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 (RS) of 25 or less: SWOG S1007.1
Rationale: Results from the TAILORX trial showed that postmenopausal women with node negative hormone receptor positive breast cancer with RS < 25 can safely forgo chemotherapy, with some benefit from chemotherapy found in patients less than 50 years with RS between 16 and 25.2 SWOG S1007 sought to determine if patients with low risk node positive (1-3 LN+), HR +, HER2 negative tumors with RS < 25 could also safely forgo chemotherapy and be managed with endocrine therapy alone.
Study design: Eligible women with HR+, HER2- breast cancer with 1-3 LN (Nmic was allowed later) positive breast cancer with RS between 0-25 were randomized between chemotherapy followed by endocrine therapy (C+ET) versus endocrine therapy (ET) alone. CT regimens not allowed included AC alone or CMF. Stratification factors included RS 0-13 vs 14-25, menopausal status, and type of axillary surgery (ALND vs SLND). The primary objective was to determine the effect of chemotherapy on invasive disease-free survival (IDFS) in patients with 1-3 LN+ breast cancer with RS < 25 and assess if this effect depended on RS. The study was set up such that if this interaction between chemotherapy and RS was not significant then the co-primary endpoint would be to determine if chemotherapy and RS are independently prognostic of IDFS, adjusting for menopausal status.
Results: 5,083 eligible patients were randomized between the two arms (ET vs C+ET). 50% of those randomized to CT received TC regimen. Only 16% in the ET and 3% in C+ET arm received ovarian suppression. Primary analysis showed that RS does not predict for benefit from chemotherapy, hence no interaction was observed. But both RS and chemotherapy were independently predictive of IDFS. For the overall population the 5 year-IDFS for C+ET arm was 92.4% and 91% for ET arm (p=0.026). When analyzed based on menopausal status, there was no difference in 5year-IDFS and overall survival between the two arms in postmenopausal women. But in premenopausal women there was an absolute difference of 5.2% in 5 year-IDFS favoring C+ET arm (p=.0004). Overall survival among premenopausal women were excellent in both arms with a 1.3% absolute benefit favoring C+ET arm (p=.032). Additional follow up will be reported in the future.
Conclusion and discussions: Results showed that in postmenopausal women with 1-3 lymph nodes and RS 0-25, we can safely forgo adjuvant chemotherapy without impacting IDFS. But the study did show that in premenopausal women with 1-3 lymph nodes and RS 0-25, there may be a significant benefit from chemotherapy. Interestingly this benefit was seen more in premenopausal patients less than 50 and in low grade tumors. Hence, whether the benefit seen in premenopausal women is due to chemotherapy induced menopause as opposed to direct cytotoxic effect is a relevant question unanswered at present. Additionally, data from the West German Study Group (WSG-Adapt HR+) presented at SABCS showed that for patients with N1 disease and RS < 12, the disease-free survival was excellent on endocrine therapy alone irrespective of age.3 This suggests that even in premenopausal patients with low risk, N1 disease and RS <12, a reasonable and effective option is the use of ovarian suppression plus ET alone.
1 Kalinsky, K. et al. Oral Presentation: [GS3-00]. San Antonio Breast Cancer Symposium; December 2020.
2JA Sparano et al. N Engl J Med 2018;379:111-121
3Harbeck, N. et al. Oral Presentation: GS4-04. San Antonio Breast Cancer Symposium; December 2020