FDA Green Light for Companion Diagnosis for Adjuvant Endocrine Therapy Abemaciclib Plus in High-Risk Early Breast Cancer

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The FDA has approved the Ki-67 IHC MIB-1 pharmDx assay to help determine which patients with early breast cancer who are at high risk of disease recurrence may benefit from adjuvant therapy with abemaciclib in combination with a endocrine treatment.

The FDA has approved the Ki-67 IHC MIB-1 pharmDx (Dako Omnis) assay to help determine which patients with early breast cancer who are at high risk of disease recurrence could benefit from adjuvant therapy with abemaciclib (Verzenio) plus hormone therapy.1

This is the first immunohistochemistry test measuring Ki-67 expression to receive regulatory approval for treatment with abemaciclib, according to Agilent Technologies, Inc. The test was developed in collaboration with Eli Lilly and Company.

Agilent’s Ki-67 IHC MIB-1 pharmDx (Dako Omnis) Companion Diagnostic Test for the Dako Omnis Advanced Staining Platform has been designed and tested to help assess the risk of recurrence in early breast cancer ”Sam Raha, president of Diagnostics and Genomics Group at Agilent Technologies, Inc., said in a press release. “Its approval sets a clinically relevant standard for assessing the risk of recurrence in early breast cancer so that more high-risk patients who may benefit clinically from treatment with [abemaciclib] are identified.

On October 12, 2021, the FDA Approved Abemaciclib and Hormone Therapy as tamoxifen or an aromatase inhibitor (IA) for the adjuvant treatment of adult patients with early-onset hormone receptor positive, HER2-negative, ganglionic breast cancer who are at high risk of recurrence and who have a Ki-67 score of 20% or more.2

The monarchE, open-label, global phase 3 trial (NCT03155997) enrolled patients 18 years of age or older with HER2-negative hormone receptor disease. Patients should be considered high risk, defined as having at least 4 positive pathologic axillary lymph nodes or 1-3 positive axillary lymph nodes and at least 1 of the following: tumor size of 5 cm or more, histologic grade 3, or a centrally assessed Ki-67 score of 20% or more.3

Patients were allowed to have received up to 12 weeks of endocrine therapy prior to randomization. Radiotherapy, as well as adjuvant and neoadjuvant chemotherapy, were authorized. If patients had occult breast cancer, metastatic disease, or disease without lymph node involvement, they were excluded. Following a modification of the protocol, patients with inflammatory disease were also excluded.

Other exclusion criteria included having received endocrine therapy for the prevention of breast cancer, raloxifene (Evista) and / or a CDK4 / 6 inhibitor, and a history of venous thromboembolic events.

A total of 5,637 patients were included in the trial, and they were randomized 1: 1 to receive either abemaciclib plus hormone therapy (n = 2,794) or endocrine therapy alone (n = 2,797). The primary endpoint of the trial was invasive disease-free survival (iDFS). A key secondary endpoint was distant relapse-free survival. Other endpoints included overall survival (OS), safety, pharmacokinetics, and patient-reported outcomes.

The basic characteristics were found to be well balanced between the 2 treatment arms. The median age of participants was 51.0 years, with 12.6% of patients under 40. Most of the patients were female (99.4%) and postmenopausal at the time of diagnosis (56.5%). In addition, 60% of patients had 4 or more positive nodes.

In addition, 95.4% of patients had received radiotherapy and 95.4% had previously received chemotherapy. Of those who received chemotherapy, 37.0% received it in the neoadjuvant setting, 58.3% in the adjuvant setting and 3.5% received it in both settings. In 68.3% of patients, IA was received as the first endocrine treatment of study treatment; this includes 14.2% of patients who received AI with ovarian function suppression (OFS). Tamoxifen was received by 31.4% of patients; 7.6% of these patients received tamoxifen and OFS.

The data that led to the approval showed that among 2003 patients with a high risk of recurrence and a Ki-67 score of 20% or greater, adding the CDK4 / 6 inhibitor to hormone therapy resulted in a significant improvement in iDFS (HR, 0.626; 95% CI: 0.488-0.803; P = .0042). The 36-month iDFS rate was 86.1% (95% CI, 82.8% -88.8%) in the investigation arm versus 79.0% (95% CI, 75.3 % to 82.3%) in the control arm.

SG data was not mature at the time of iDFS analysis.

Regarding safety, the most common toxicities reported in the trial were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.

The references

  1. Agilent Receives FDA Companion Diagnostic Approval for Ki-67 IHC MIB-1 pharmDx in High-Risk Early Breast Cancer. Press release. Agilent Technologies, Inc. October 13, 2021. Accessed October 14, 2021. https://bwnews.pr/3FHKHFn
  2. The FDA approves abemaciclib with endocrine therapy for early breast cancer. Press release. FDA. October 13, 2021. Accessed October 14, 2021. https://bit.ly/2YMIiIn
  3. Johnson SRD, Harbeck N, Hegg R, et al. Abemaciclib in combination with hormone therapy for the adjuvant treatment of early Hr +, HER2-, lymph node, high risk (monarchE) breast cancer. J Clin Oncol. 2020; 38 (34): 3987-3998. doi: 10.1200 / JCO.20.02514


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