Gene expression analysis reveals MammaPrint® as the only commercially available genomic signature that may identify patient subgroups with resistance to CDK4/6 inhibition

New real world evidence from FLEX adds to the growing body of data demonstrating MammaPrint and BluePrint® utility in predicting response to neoadjuvant chemotherapy in HR+HER2- breast cancer

IRVINE, Calif. & AMSTERDAM–(BUSINESS WIRE)–Agendia®, Inc., today announced it will be presenting new data highlighting MammaPrint® and BluePrint® utility in guiding treatment decisions for patients with early-stage breast cancer. The findings will be presented in two spotlight presentations and two posters at the San Antonio Breast Cancer Symposium 2024 (SABCS), on Wednesday, December 11th and Thursday, December 12th.

One poster spotlight, titled “Association of MammaPrint® with gene expression pathways predictive of resistance to cyclin-dependent kinase inhibition,” presented by Adam Brufsky, MD, PhD, Professor and Associate Chief of Hematology and Oncology at UPMC Hillman Cancer Center, examined 5,657 patients with early-stage HR+HER2- tumors enrolled in the ongoing prospective, observational FLEX Trial (NCT03053193). The analysis evaluated the correlation between MammaPrint and gene expression patterns associated with Retinoblastoma (Rb) loss-of-function and CDK4 independent cellular proliferation to identify which MammaPrint Risk categories may be resistant to CDK4/6 inhibition.

A linear correlation was observed between increasing MammaPrint Risk and increasing Rb loss-of-function gene expression, suggesting that MammaPrint High 2 tumors have the highest probability of CDK4/6 resistance. Additionally, MammaPrint High 2 tumors were most likely to exhibit high cell proliferation independent of CDK4 activity (43.0%), in comparison to Ultra Low (0.1%), Low (0.5%), and High 1 (1.8%) tumors (p < 0.001). These data provide the first evidence for the utility of a commercially available signature to potentially predict resistance to CDK4/6 inhibition and help patients receive more targeted and individualized therapies.

The second poster spotlight, titled “MammaPrint® and BluePrint® Predict Pathological Response to Neoadjuvant Chemotherapy in Patients with HR+HER2- Early-Stage Breast Cancer Enrolled in FLEX,” presented by Joyce O’Shaughnessy, MD, National Principal Investigator of the FLEX Study, Director, Breast Cancer Research, Baylor University Medical Center, Texas Oncology and the Sarah Cannon Research Institute in Dallas, TX, evaluated MammaPrint and BluePrint in predicting pathological response to neoadjuvant chemotherapy among 457 HR+HER2- breast cancer patients enrolled in FLEX.

Rates of Pathological Response (PR), including pathological Complete Response (pCR) and minimal residual cancer burden (RCB-I), were highest in High 2 Basal (43.4%) and Luminal B (21.4%) tumors, with High 2 tumors overall showing better PR rates (32.7%) compared to High 1 tumors (9.5%). Multivariate analysis indicated that only MammaPrint High 2 was significantly associated with likelihood of PR, after adjusting for clinical confounders. Overall, MammaPrint and BluePrint proved effective in predicting neoadjuvant chemosensitivity in HR+HER2- breast cancer, which may enable downstaging and improve overall outcomes.

“The findings from these two studies highlight the ability of genomic testing using MammaPrint and BluePrint to predict patient response to therapies like chemotherapy, and may be able to predict benefit from CDK4/6 inhibitors,” said Dr. O’Shaughnessy. “The ongoing data that continues to be generated through FLEX is building evidence that these tests may help unlock optimal treatment plans based on the patient’s tumor biology.”

Abstracts Accepted as Posters

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine – Biology is Still King (Rahman, R., et al.)

A pooled analysis was conducted on 404 clinical T3 breast cancer patients from the NBRST, FLEX, and MINT trials undergoing neoadjuvant chemotherapy. MammaPrint (MP) and BluePrint (BP) subtyping showed higher pathological complete response (pCR) rates across all MP High Risk subtype tumors (Basal (32.5%, HER2 53.7%, Luminal B 8.6%) compared to MP Low Risk Luminal A subtype tumors (0% pCR). Menopausal status, nodal status, and grade were not significant predictors of pCR response. High Risk tumors had significantly higher pCR rates, suggesting MammaPrint Low Risk, cT3 tumors are unlikely to achieve pCR to neoadjuvant chemotherapy, suggesting these patients may avoid neoadjuvant chemotherapy despite their large tumor size.

FLEX: A Real-World Evidence, Full Transcriptome Study in 30,000 Patients with Early-Stage Breast Cancer (Maganini, R., et al.)

The FLEX Study, a large, multi-center, real-world evidence, whole transcriptome, observational breast cancer study (NCT03053193), has grown substantially since its launch in April 2017. With more than 17,000 patients enrolled across 100 sites in the US and around the world, FLEX includes over 40 sub-studies in several topics. Participants are of all racial and ethnic backgrounds with stage I, II, or III early-stage breast cancer, aiming for a representative data set. The study has produced more than 10 clinical evidence pieces on diversity and includes 1,377 self-identified Black, 530 Latin American/Hispanic, and 353 Asian and Pacific Islanders, making FLEX the most diverse study on EBC patients to date.

“These data significantly enhance our understanding of MammaPrint and BluePrint’s growing clinical applications,” said William Audeh, MD, MS, Chief Medical Officer at Agendia. “Our findings reinforce the importance of precision medicine, as it allows us to tailor treatment strategies, including neoadjuvant chemotherapy consideration, incorporating immunotherapies, and potentially sparing patients from the harms of unnecessary chemotherapy. As we continue to gather data from studies like FLEX, we are solidifying the role of these genomic assays in guiding personalized treatment decisions for breast cancer patients.”

About Agendia

Agendia is a leading provider of innovative solutions in the field of precision oncology. With a focus on early-stage breast cancer, Agendia offers reliable biological insights that inform personalized treatment decisions for patients and their care teams. Their advanced genomic assays, MammaPrint® + BluePrint®, enable clinicians to quickly identify the most effective treatment plan, minimizing the risk of both under- and over-treatment.

Agendia was founded in 2003 and is headquartered in Amsterdam with its state-of-the-art laboratory facility located in Irvine, CA. Led by world-renowned scientists and oncologists, Agendia is committed to advancing genomic insights through ongoing research. This includes the notable FLEX Study – the world’s largest whole transcriptome Real-World Evidence-based Breast Cancer database which aims to revolutionize precision in breast cancer management. With cutting-edge technology, research and innovation, Agendia strives to shape the future of precision oncology and make a significant impact in the fight against breast cancer.

About MammaPrint

MammaPrint® is a gene expression profiling test that reveals the distinct underlying biology of an early-stage tumor to determine its risk of spreading. As the only FDA-cleared gene expression profiling test to assess a woman’s risk of distant metastasis, MammaPrint® provides critical answers that help inform the future of her treatment plan at the point of diagnosis, including the timing and benefit to chemotherapy and endocrine therapy. MammaPrint® listens to the signals from 70 key genes in a woman’s tumor to stratify her risk within four distinct categories – ranging from UltraLow, Low, High 1, and High 2– to fuel a right-sized care plan tailored to her biology and her life’s plans.

About BluePrint

BluePrint® is a gene expression profiling test that reveals the driving forces behind a tumor’s growth at the earliest stage possible in a woman’s breast cancer care journey to help optimize and personalize treatment planning. As the only molecular subtyping test available in the U.S., BluePrint® goes where pathology cannot, offers critical insights that providers may otherwise have not known to act on, and gives women the best chance to return to a life not defined by cancer. BluePrint® measures the activity of 80 key genes that are involved in a tumor’s growth to classify a tumor as Luminal-type, HER2-type, or Basal-type, each of which warrant distinct treatment pathways. By revealing the distinct underlying biology of a woman’s tumor, BluePrint® can catch often misclassified, yet highly aggressive, Basal tumors, so women can be prescribed the most appropriate treatment from the start.

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ICR Healthcare PR

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Terri.Clevenger@ICRHealthcare.com