ONCOLOGY
OBSTETRICS & GYNECOLOGY
CONFERENCE UPDATE

OPTIMA trial: Multigene expression assay safely guides chemotherapy decisions in high-risk ER+/HER2- eBC

3 Nov 2026

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STUDY DESIGN​

Tumor expression assays are widely used to guide adjuvant chemotherapy decisions in estrogen receptor-positive (ER+), HER2-negative (HER2-) early breast cancer (eBC) with limited nodal involvement.1 However, prospective evidence remains limited in patients at higher clinical risk, including premenopausal patients and those with greater nodal involvement.1 The phase 3 OPTIMA trial evaluated whether the 50-gene Prosigna Risk of Recurrence (ROR) assay-guided treatment could reduce adjuvant chemotherapy use without compromising clinical outcomes.1

Eligible patients were adults aged ≥40 years with completely excised ER+ (immunohistochemistry >10%), HER2- eBC, 0-9 involved axillary lymph nodes, or node-negative tumors >30mm.1 A total of 4,429 patients were randomized 1:1 to standard chemo-endocrine therapy (CET) or a Prosigna-guided treatment strategy.1 In the test-directed arm, patients with ROR >60 received CET, whereas those with ROR ≤60 received endocrine therapy (ET) alone.1 ROR scores were not disclosed, and patients receiving CET were blinded to treatment allocation.1

The primary outcome assessed was invasive breast cancer-free survival (IBCFS), defined as local, regional, or distant recurrence, second primary breast cancer, or death from any cause.1 Noninferiority was assessed in the per protocol population using a prespecified 3% absolute margin after ≥1 year of follow-up.1 Key secondary analysis evaluated IBCFS among patients with low-risk tumors (ROR ≤60) using a 3.5% noninferiority margin.1

Among the 4,153 patients included in the per-protocol population, baseline characteristics were generally balanced between treatment groups, with a median age of 56 years and 37% of patients being premenopausal.1 Approximately two-thirds of patients had low-risk tumors according to the Prosigna assay, with ROR ≤60 observed in 66.0% of the control arm and 67.8% of the test-directed arm.1

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FINDINGS

Primary outcome:
  • The primary outcome assessed was IBCFS, with noninferiority assessed in the per-protocol population using a prespecified 3% absolute margin1
  • At a median follow-up of 4.0 years, the test-directed strategy demonstrated noninferiority to standard care for IBCFS in the overall per-protocol population (adjusted HR=1.03; 90% CI: 0.85-1.25; p=0.006 for noninferiority)1
  • Five-year IBCFS rates were 91.8% in the control arm and 90.3% in the test-directed arm, corresponding to an absolute difference of 1.5%, which remained within the predefined noninferiority margin1
Key secondary outcome:
  • Key secondary analysis evaluated IBCFS among patients with low-risk tumors (ROR ≤60) using a 3.5% noninferiority margin1
  • In patients with low-risk tumors (ROR ≤60), the test-directed strategy also met the prespecified criterion for noninferiority (adjusted HR=1.06; 90% CI: 0.80-1.40; p=0.003 for noninferiority)1
  • Five-year IBCFS rates were 94.8% in the control arm and 93.6% in the test-directed arm, representing an absolute difference of 1.2%, which remained within the prespecified noninferiority margin1
  • Subgroup analyses demonstrated generally consistent findings across menopausal status, tumor grade, tumor size, nodal involvement, disease stage, and intended chemotherapy regimen, with no subgroup showing a clear differential treatment effect1
  • Distant recurrence-free interval was similarly maintained between treatment groups in both the overall per-protocol population (adjusted HR=1.04; 90% CI: 0.83-1.30) and the ROR ≤60 subgroup (adjusted HR=1.17; 90% CI: 0.82-1.66)1
  • Sensitivity analyses in the intention-to-treat population yielded results consistent with the primary per-protocol analysis, supporting the robustness of the findings1

 

“The 50-gene test can assist safe adjuvant chemotherapy decisions for premenopausal women aged at least 40 years treated with ovarian function suppression and patients with 4-9 involved lymph nodes or stage IIIA tumors”

Professor Robert C. Stein
University College London Cancer Institute,
London, United Kingdom

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References

  1. Stein RC, et al. First results from the OPTIMA phase III randomized non-inferiority trial of test-directed chemotherapy in patients with high clinical risk ER-positive HER2-negative early breast cancer: A pre-planned time-driven analysis. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2026; May 29-June 2, 2026.

ESTROGEN RECEPTOR-POSITIVE
OPTIMA TRIAL
BREAST CANCER

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