Clinical evidence for the Oncotype DX® test in node-positive patients

The Recurrence Score® result has been proven to be predictive of chemotherapy benefit for HR+, HER2-, node-positive postmenopausal patients in the retrospective SWOG-8814 study.1 The prospective randomised trial RxPONDER including more than 5 000 patients was designed to refine chemotherapy benefit estimates for HR+, HER2- patients with Recurrence Score results 0-25 with 1 to 3 positive nodes.3 Initial results of the RxPONDER study have been described as practice-changing.3-5

  • The majority of N1 postmenopausal patients may be spared chemotherapy based on Recurrence Score® results 0-25, independent of clinical pathological parameters3-5
  • N1 premenopausal patients with Recurrence Score results 0-25 have a modest 2.4% benefit from chemotherapy in terms of distant recurrence-free interval at 5 years4

Clinical Evidence

SWOG-8814 study

The retrospective analysis of the SWOG-8814 trial, in which HR+, node-positive, postmenopausal patients were randomised to chemoendocrine therapy vs endocrine therapy alone, established that the Recurrence Score result is predictive of chemotherapy benefit in node-positive patients1, consistent with the findings in the node-negative setting in the NSABP B-20 clinical trial.6-7

The Recurrence Score® result was a strong predictive factor of chemotherapy benefit for disease-free survival (P interaction = 0.029), overall survival and breast cancer-specific survival in the first five years.1

RxPONDER trial

RxPONDER (SWOG S1007) is an ongoing prospective, randomised trial to determine the effect of chemotherapy in patients with hormone receptor-positive (HR+), HER2-negative breast cancer with 1-3 positive axillary lymph nodes, including micrometastases.3-5 For this purpose, eligible patients with Recurrence Score® (RS®) results 0-25 were randomised to adjuvant chemotherapy followed by endocrine therapy or to endocrine therapy alone.3-5

RxPONDER study design: node-positive (1-3 nodes) patients with Recurrence Score results 0–25 were randomised to endocrine therapy alone or chemoendocrine therapy3-5


At a prespecified interim analysis in September 2020, the Data Safety Monitoring Committee advised the study investigators to report the available findings of the clinical trial. Results were presented at the San Antonio Breast Cancer Symposium in 2020 and 2021 as well as published in The New England Journal of Medicine in December 2021.3-5 A total of 5,018 patients were included in the analysis with a 6.1-year median follow up in the latest report.

Postmenopausal patients

Stratified by menopausal status, 5-year distant recurrence-free interval (DRFI) was similar for postmenopausal patients treated with endocrine therapy with or without chemotherapy (hazard ratio 1.12; 95% CI 0.82 to 1.52; p=.49).4 The lack of benefit from chemotherapy was observed regardless of clinicopathological factors such as patient age, tumour grade, tumour size, number of positive nodes, type of surgery, or Recurrence Score group (RS results 0-13 vs results 14-25).3-5 No significant difference in invasive disease-free survival (IDFS), distant relapse-free survival (DRFS) or overall survival (OS) was observed.3-5

Based on this interim analysis, the authors concluded that the majority of N1 postmenopausal patients do not benefit from adjuvant chemotherapy, independent of clinical pathological parameters and thus can likely forgo adjuvant chemotherapy based on Recurrence Score® results 0-25.3-5

N1 postmenopausal patients with RS® results 0-25 did not benefit from the addition of chemotherapy to endocrine therapy on any endpoint reported4

Premenopausal patients

For premenopausal patients, 5-year distant recurrence-free interval (DRFI) differed significantly by treatment (chemotherapy hazard ratio 0.64; 95% CI 0.43 to 0.95; p=.026),4 with a 2.4% absolute difference in rate of distant recurrence-free interval. The benefit of chemotherapy was observed regardless of clinicopathological factors such as patient age, tumour grade, tumour size, number of positive nodes and type of surgery. Chemotherapy benefit by Recurrence Score group (RS 0-13 and RS 14-25) was 2.3% and 2.8%, respectively.4

Based on this interim analysis, the authors suggested that premenopausal patients with N1 breast cancer and Recurrence Score results 0-25 have a modest benefit from adjuvant chemotherapy. 3-5

N1 premenopausal patients with RS® results 0-25 have a modest benefit from the addition of chemotherapy with a 2.4% benefit in terms of 5-year distant recurrence-free interval3-5

ABBREVIATIONS

CET=chemo-endocrine therapy
CI=confidence interval
CT=chemotherapy
DDFS=distant-disease free survival
ER= Endocrine therapy
HER2–=human epidermal growth factor receptor 2 negative
HR+=hormone receptor positive
N+=node-positive
N0=node-negative
N1mi=lymph node micrometastases
N1=1–3 positive nodes
RS=Recurrence Score result
RxPONDER=Rx for Positive Node, Endocrine Responsive Breast Cancer
TAILORx=Trial Assigning IndividuaLized Options for Treatment (Rx)

REFERENCES

  1. Albain et al. Lancet Oncol. 2010.
  2. SWOG. Press release. 2020.
  3. Kalinsky et al. SABCS. 2020 GS3-00.
  4. Kalinsky et al. SABCS. 2021 GS2-07.
  5. Kalinsky. N Eng J Med. 2021.
  6. Paik et al. J Clin Oncol. 2006.
  7. Geyer et al. NPJ Breast Cancer. 2018.
  8. Stemmer et al. NPJ Breast Cancer. 2017.
  9. Hortobagyi et al. SABCS. 2018.
  10. Nitz et al. Breast Cancer Res Treat. 2017.
  11. Paik et al. N Engl J Med. 2004.
  12. Sparano et al. N Engl J Med. 2018.
  13. Dowsett et al. J Clin Oncol. 2010.
  14. Petkov et al. NPJ Breast Cancer. 2016.
  15. IQWiG. Press release. 2018.
  16. Andre et al. J Clin Oncol. 2019.
  17. NCCN Guidelines. 2021.
  18. NICE. 2018.
  19. Burstein et al. Ann Oncol. 2019.
  20. Cardoso et al. Annals of Oncology. 2019.
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