Node-Positive and Node-Negative Evidence | Oncotype DX Test

Node-Negative

The clinical validity and utility of the Oncotype DX Breast Recurrence Score^® test in patients with HR+, HER2-, node-negative, early-stage, invasive breast cancer have been established through extensive clinical research in over 85,000 patients.^1-8

The Oncotype DX Breast Recurrence Score test was validated as prognostic of distant recurrence for node-negative, HR+ early stage breast cancer patients¹
The Oncotype DX^® test was uniquely validated to predict chemotherapy benefit in the 2-arm randomised clinical trial NSABP B-20^2,9 (interaction between Recurrence Score® result and benefit from chemotherapy p=0.014⁹).
The practice-changing TAILORx prospective randomised clinical trial refined former findings, enabling a more precise threshold for CT benefit.^3,4,10

Oncotype DX clinical evidence in node-negative patients - prediction of chemotherapy benefit makes the Oncotype DX Breast Recurrence Score test unique.

Clinical evidence from the TAILORx and NSABP B-20 studies established that the Oncotype DX test can identify two groups of patients: those who may be spared chemotherapy and those who may substantially benefit from it.^2,4,9

Oncotype DX clinical evidence in node-negative patients - TAILORx and NSABP B-20 studies - who may be spared chemotherapy and who may substantially benefit from it.

Patients with Recurrence Score results 0–25 do not benefit from the addition of chemotherapy to endocrine therapy^2,4,9

Patients with Recurrence Score results 26–100 significantly benefit from the addition of chemotherapy to endocrine therapy^2,9

The NSABP B-20 trial established that patients with Recurrence Score results 0-10 do not benefit from the addition of CT to ET and that patients with a Recurrence Score result 26-100 do benefit from the addition of CT9. The TAILORx trial was designed to determine whether ET was non-inferior to CT+ET in patients with Recurrence Score results 11-25.^4,11

Oncotype DX clinical evidence in node-negative patients - TAILORx landmark practice-changing trial - patients with Recurrence Score results 11-25.

The TAILORx study met its primary and secondary endoints: patients with Recurrence Score results 11-25 treated with chemoendocrine therapy had similar rates of clinical events to patients receiving endocrine therapy alone in non-inferiority design invasive disease-free survival (primary endpoint), distant recurrence-free interval and overall survival.⁴

Real-world evidence is consistent with clinical studies. It confirms that the Oncotype DX test consistently identifies a minority of patients (15-20%) with Recurrence Score results 26-100 who derive substantial benefit from chemotherapy.

The Oncotype DX Breast Recurrence Score test identifies the vast majority of women who may not benefit from the addition of chemotherapy to endocrine therapy and the important minority of women for whom chemotherapy may be life-saving.^2,4,9

The only assay proven to predict chemotherapy benefit²

Independent predictor of chemotherapy benefit and patient outcomes²

Can help reduce over- and undertreatment^4,14-18

Can help guide treatment decisions across age groups⁴

Consistent and large body of evidence across prospective randomised trials, validation studies and real-world evidence^1-10

The first clinical validation of the Oncotype DX Breast Recurrence Score test, the NSABP B-14 study, demonstrated that the Recurrence Score result quantifies the risk of distant recurrence in node-negative patients. It showed that the 10-year rate of distant recurrence is significantly lower for patients with low Recurrence Score results compared to patients with higher scores.

This study determined that the Oncotype DX Breast Recurrence Score test predicts the likelihood of chemotherapy benefit for node-negative patients: a low Recurrence Score result predicted little to no benefit from the addition of chemotherapy to endocrine therapy, while a high score predicted a larger benefit from chemotherapy.

The first prospective outcomes study providing Level 1A evidence for a multigene assay, the TAILORx Trial confirmed that, overall, patients with Recurrence Score results 11-25 do not benefit from the addition of chemotherapy to endocrine therapy and may be effectively and safely treated with hormonal therapy alone.

Abbreviations

CI, confidence interval
CT, chemotherapy
ET, endocrine therapy
HER2–, human epidermal growth factor receptor 2 negative
HR+, hormone receptor positive
HR, hazard ratio
N0, node-negative
RS, Recurrence Score result
SEER, Surveillance, Epidemiology and End Results program
TAILORx, Trial Assigning IndividuaLized Options for Treatment (Rx)

References

Paik et al. N Engl J Med. 2004.
Paik et al. J Clin Oncol. 2006.
Sparano et al. N Engl J Med. 2015.
Sparano et al. N Engl J Med. 2018.
Dowsett et al. J Clin Oncol. 2010.
Nitz et al. Breast Cancer Res Treat. 2017.
Hortobagyi et al. SABCS 2018. Poster P3-11-02.
Stemmer et al. npj Breast Cancer. 2017;3:32 and 2017;3:33.
Geyer et al. npj Breast Cancer 2018.
Sparano et al. SABCS 2022. Abstract GS1-05
Sparano and Paik. J Clin Oncol. 2008.
Sparano et al. N Engl J Med. 2019.
Bello et al. Ann Surg Oncol. 2018
Battisti et al. St Gallen International conference 2019, P007.
Thill et al. EBCC 2020. Poster 367.
Cognetti et al. npj Breast. 2021.
McSorley et al. J Clin Oncol. 38 : 2020(suppl ; abstr 540).
Curtit et al. Breast. 2019.

Node-Positive

The Oncotype DX^® test 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 and 1 to 3 positive nodes.² Initial results of the RxPONDER study have been described as practice-changing.³

The majority of N1 postmenopausal patients may be spared chemotherapy based on Recurrence Score^® results 0-25, independent of clinical pathological parameters^2,4
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

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.^5,6

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.^2,4 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.^2,4

The Oncotype DX Breast Recurrence Score test identifies the vast majority of women who may not receive a benefit from chemotherapy and can ultimately be spared chemotherapy.¹

The only assay proven to predict chemotherapy benefit¹

Independent predictor of chemotherapy benefit and patient outcomes^1,2

Can help reduce over- and undertreatment^8-13

Can help guide treatment decisions across age groups²

Consistent and large body of evidence across prospective randomised trials, validation studies and real-world evidence^{1,2,4-8,14,15}

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

Albain et al Lancet Oncol. 2010.
Kalinsky et al. N Eng J Med. 2021.
SWOG. Press release. 2020
Kalinsky et al. SABCS. 2021 GS2•07.
Paik et al J Clin Oncol 2006.
Geyer et al. npj Breast Cancer. 2018.
Kalinsky et al. SABCS. 2020 GS3-00.
Sparano et al. N Engl J Med. 2018.
Battisti et al. St Gallen International conference 2019, P007.
Thill et al. EBCC 2020. Poster 367.
Cognetti et al. npj Breast. 2021.
McSorley et al. J Clin Oncol. 38 : 2020(suppl ; abstr 540).
Curtit et al. Breast. 2019.
Stemmer et al NPJ Breast Cancer. 2017.
Hortobagyi et al. SABCS. 2018.

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Clinical evidence

More information on TAILORx​

References

Abbreviations

References

SWOG-8814 study​

References

RxPONDER trial​

References

Abbreviations

References

More information on TAILORx

SWOG-8814 study

RxPONDER trial