Circulating Tumor Cells Isolated With Unique TellDx Technology May Help Predict Response to Therapy in Patients With Progressive Metastatic Breast Cancer
TellBio, Inc. recently announced publication of data that show the utility of CTCs isolated with TellDx to assess sensitivity and potential clinical benefit from an alternative tolerable therapeutic option in a cohort of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) who progress on endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6 inhibition (CDK 4/6i). The paper, titled A Gene Panel Associated With Abemaciclib Utility in ESR1-Mutated Breast Cancer After Prior Cyclin-Dependent Kinase 4/6-Inhibitor Progression, was published in JCO Precision Oncology (DOI 10.1200/PO.22.00532).
“These data demonstrate that live CTCs, isolated by the TellDx System, may be used to elucidate mechanisms of resistance and sensitivity to alternative treatments and personalize patient management by identifying tailored therapies for a subset of patients with metastatic breast cancer experiencing progression on standard of care therapies,” said Pritesh J. Gandhi, PharmD, CEO, TellBio, Inc.
Currently, patients with HR+/HER2- metastatic breast cancer (mBC) receive endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) as first line treatment. Within this cohort, patients can experience disease progression due to resistance to ET, CDK4/6i, or both. Standard of care for patients with HR+/HER2- mBC who progress due to estrogen receptor 1 (ESR1) mutations has not been established, and this constitutes an active area of clinical and translational exploration. Thus, there is an unmet need to develop biomarkers for response to guide treatment decisions among patients with acquired ESR1 pathogeneic mutations.
The aim of this multicenter retrospective study was to the assess the effect of abemaciclib, a CDK4/6i with unique pharmacokinetic and pharmcodynamic properties, in breast cancer cell lines, patient-derived CTCs isolated with the TellDx technology, and patients with HR+/HER2- mBC. CTCs were studied to gain insights into the role of ESR1 mutations and response to abemaciclib. CTCs were treated with select doses of endocrine therapy, fulvestrant or abemaciclib. CTC-derived cultures with ESR1 mutation were noted to have increased sensitivity to abemaciclib compared to CTC lines with CDKi-resistance mutations. Among patients with ESR1 pathogenic alterations who progressed on ET plus CDK4/6 inhibitor, palbociclib, and who had received abemaciclib, the median PFS was 7.0 months (95% CI, 4.1-13.2 months) in patients without CDK4/6i resistance (CDKiR[-]) (n=17) compared to 3.5 months (95% CI, 2.1-5.4 months) in patients with CDK4/6i resistance (CDKiR[+]) (n=11); p=0.02. In the post-palbociclib setting, administration of abemaciclib resulted in a two-fold longer PFS in patients with CDKi-R(-) compared to patients with CDKi-R(+).
“This work represents an important step forward as we strive to develop a novel genomic and molecular biomarker to aid in therapy selection for patients with metastatic breast cancer. Our ability to isolate circulating tumor cells and develop models of drug sensitivity and resistance in the laboratory fosters critically important validation of findings from the clinic. Bedside-to-bench research efforts like these have tremendous potential to unlock new insights into drug resistance and deliver upon the promise of precision medicine in oncology,” said Seth Wander, MD, PhD, Massachusetts General Hospital.
This translational research effort expands upon the first study which demonstrated sensitivity to and clinical utility of abemaciclib after progression on palbociclib. These data show that CTCs may be leveraged to assess sensitivity and shed light on potential clinical benefit from an alternative tolerable therapeutic option in a cohort of patients with HR+/HER2- mBC with ESR1 mutations who progress on CDK4/6i, which can potentially delay the need for toxic chemotherapy. The CTC biomarker strategy can be extended to the adjuvant or first-line metastatic populations and additional efforts will explore CTCs as a pre-specified prognostic surrogate to guide rational therapy selection.
TellBio is a development-stage biotechnology company focused on revolutionizing the detection of cancer metastasis through its unique and proprietary CTC technology, TellDx. TellDx, the already fully functional diagnostic solution, isolates live CTCs from patient liquid biopsies. The platform has been developed and optimized following a decade of research and development. TellDx offers a unique opportunity to isolate CTCs via its microfluidic diagnostic platform to advance translational and clinical efforts and optimize the lives of patients with cancer.
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