FLEX Study data shows that patients with MammaPrint High Risk 2 tumors have improved 3-year survival with anthracycline-containing regimens, while patients with High Risk 1 tumors show no additional benefit
IRVINE, Calif. & AMSTERDAM--(BUSINESS WIRE)--Agendia®, Inc., a leader in precision oncology for breast cancer, today announced the publication of a new paper in JCO Precision Oncology, titled “Prediction of Anthracycline Benefit in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Early-Stage Breast Cancer by the MammaPrint 70-Gene Signature for Patients Enrolled in the FLEX Study.”
The study, based on data from the prospective, real-world FLEX Study (NCT03053193), found that MammaPrint® + BluePrint® can help identify a subset of patients with hormone receptor positive, HER2-negative (HR+HER2-) early-stage breast cancer (EBC) most likely to benefit from anthracycline-based chemotherapy. This research led to an update in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recognizing MammaPrint as the only genomic test to guide personalized anthracycline use in this patient population.
“Patients with HR+HER2-negative breast cancer who are candidates for adjuvant chemotherapy continue to face uncertainty around whether they will derive meaningful benefit from anthracycline-containing regimens,” said Joyce O’Shaughnessy, M.D., principal investigator for the FLEX Study. “This long-standing clinical dilemma underscores the need for predictive biomarkers that can identify which patients are most likely to benefit from anthracyclines and who may safely avoid unnecessary toxicity.”
While anthracyclines are highly effective antitumor agents, they are associated with potentially serious toxicities, including cardiotoxicity and secondary leukemias. Multiple randomized controlled trials – including the ABC trials1, Plan B trial2, the MASTER trial3 and the DBCG 07-READ trial4 – have attempted to determine whether anthracycline-free chemotherapy regimens are non-inferior to anthracycline-containing regimens in clinically high-risk HER2-negative EBC but found no significant difference among HR+HER2- patients.
This observational study from FLEX included 1,259 patients with stages I to III, HR+HER2- EBC, classified as MammaPrint High Risk 1 (H1) or High Risk 2 (H2) and BluePrint Luminal B, who received adjuvant chemotherapy with either anthracycline and taxane-based chemotherapy (AC-T) or adjuvant taxane with cyclophosphamide (TC), and had a median follow-up of 3.2 years. Inverse probability of treatment weighting (IPTW), a well-established statistical method for the analysis of real-world evidence, was performed to balance clinical characteristics between treatment groups and approximate the design of a randomized trial.
Key findings from the study include:
- Patients with H2 tumors demonstrated significantly improved 3-year invasive disease-free survival (IDFS) with AC-T versus TC, with IDFS rates of 100% vs 94.8%, respectively – an absolute benefit of 5.2% (p=0.023).
- Patients with H1 tumors showed no significant difference in 3-year IDFS with identical IDFS rates of 95.9% for both regimens, despite overlapping high-risk clinical features.
- A statistically significant treatment-by-MammaPrint interaction demonstrated that AC-T benefit increased with higher genomic risk (p=0.036), showing that MammaPrint H2 is predictive of anthracycline benefit.
“This study answers a question that randomized clinical trials have been unable to resolve, illustrating the value of genomic profiling to predict benefit from a specific cancer therapy,” said William Audeh, M.D., M.S., Chief Medical Officer of Agendia and co-author of the study. “The FLEX Study highlights the power of a multi-modal real-world evidence database to produce robust, clinically relevant data which not only inform treatment decisions, but also change clinical practice guidelines.”
References
1. Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC Trials—USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017;35(23):2647-55. doi:10.1200/JCO.2016.71.4147
2. Nitz U, Gluz O, Clemens M, et al. West German Study PlanB Trial: Adjuvant four cycles of epirubicin and cyclophosphamide plus docetaxel versus six cycles of docetaxel and cyclophosphamide in HER2-negative early breast cancer. J Clin Oncol. 2019;37(10):799-808. doi:10.1200/JCO.18.00028
3. Yu KD, Liu XY, Chen L, et al. Anthracycline-free or short-term regimen as adjuvant chemotherapy for operable breast cancer: A phase III randomized non-inferiority trial. Lancet Reg Health West Pac. 2021;11:100158. doi:10.1016/j.lanwpc.2021.100158
4. Ejlertsen B, Tuxen MK, Jakobsen EH, et al. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017;35(23):2639-2646. doi:10.1200/JCO.2017.72.3494.
About Agendia
Agendia is a global leader in precision oncology focused on early-stage breast cancer. The company’s genomic assays, MammaPrint + BluePrint, deliver essential biological insights to inform personalized treatment decisions for patients and their care teams. With operations in Amsterdam and Irvine, Agendia partners with academic and community oncology centers worldwide to generate real-world evidence through the landmark FLEX Study (NCT03053193), the largest whole-transcriptome registry of early-stage breast cancer.
About MammaPrint
MammaPrint is a gene expression profiling test that assesses a woman’s risk of distant metastasis in early-stage breast cancer. By analyzing 70 key genes in a tumor, it stratifies risk into four categories — UltraLow Risk, Low Risk, High Risk 1, and High Risk 2 — to help guide personalized treatment planning, including chemotherapy benefit and de-escalation decisions.
About BluePrint
BluePrint is an 80-gene molecular subtyping assay that reveals the functional biology driving tumor growth, classifying tumors as Luminal-type, HER2-type, or Basal-type. By defining intrinsic subtypes beyond traditional immunohistochemistry, BluePrint provides critical insights to optimize treatment selection and improve outcomes.
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