What side effects are associated with this type of intervention?

Common side effects of CDK4/6 inhibitors, such as Abemaciclib, include diarrhea, neutropenia (low white blood cell count), fatigue, nausea, and abdominal pain. Fulvestrant, an estrogen receptor antagonist, often causes injection site pain, hot flashes, fatigue, and nausea. Both treatments can lead to more serious but less common side effects, such as liver function abnormalities and increased risk of infections due to immunosuppression.

What prior FDA approvals exist?

The FDA has approved several CDK4/6 inhibitors for the treatment of hormone receptor-positive, HER2-negative breast cancer, similar to Abemaciclib. These include Palbociclib and Ribociclib, which are often used in combination with endocrine therapies like Letrozole or Fulvestrant. Fulvestrant itself is an FDA-approved estrogen receptor antagonist used in hormone receptor-positive metastatic breast cancer, often in combination with other agents to improve efficacy. These treatments aim to inhibit cancer cell proliferation by targeting specific pathways involved in cell cycle regulation and hormone receptor signaling.

What other types of research exist?

Promising novel alternatives to Abemaciclib and Fulvestrant for cancer treatment in 2024 include: 1) PI3K/PTEN/AKT/mTOR pathway inhibitors such as Temsirolimus and Everolimus, which have shown efficacy in hormone receptor-positive cancers. 2) Pembrolizumab, an immune checkpoint inhibitor, which has been investigated in combination with other agents like cetuximab for various cancers. 3) Olaparib, a PARP inhibitor, particularly in combination with abiraterone for cancers with homologous recombination repair deficiencies. These alternatives offer different mechanisms of action and have shown promise in clinical trials.

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CDK4/6 Inhibitor

Abemaciclib + Fulvestrant for Breast Cancer (postMONARCH Trial)

Milford, MA

Phase 3

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression

Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982)

Must not have

Have received more than 1 line of therapy for advanced or metastatic disease

Have received prior treatment with fulvestrant, any investigational estrogen receptor (ER)-directed therapy (including selective ER degraders [SERDs] and non-SERDs), any phosphatidylinositol 3-kinase (PI3K)-, mammalian target of rapamycin (mTOR)-, or protein kinase B (AKT)-inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up randomization until measured progressive disease (up to 22 months)

Awards & highlights

Pivotal Trial

Summary

This trial is testing a combination of two drugs, abemaciclib and fulvestrant, for treating a specific type of breast cancer that has not responded to previous treatments. Abemaciclib is taken orally and is approved for treating certain types of breast cancer. The goal is to see if this combination can help stop the cancer from growing. The study may last several years, depending on how well the treatment works for each patient.

See full description

Who is the study for?

This trial is for postmenopausal women with HR+, HER2- advanced or metastatic breast cancer that worsened after treatment with CDK4/6 inhibitors and endocrine therapy. They must have good organ function, measurable disease progression, be able to take oral medication, and have a performance status of 0 or 1. Women who've had chemotherapy for metastatic breast cancer or certain other treatments are excluded.Check my eligibility

What is being tested?

The study tests if adding abemaciclib to fulvestrant improves outcomes in patients whose breast cancer progressed after previous therapies. Participants will either receive the combination of abemaciclib plus fulvestrant or a placebo plus fulvestrant over up to five years, depending on their response.See study design

What are the potential side effects?

Abemaciclib may cause diarrhea, fatigue, nausea, decreased appetite and blood cell counts leading to infection risk; it can also affect liver enzymes. Fulvestrant's side effects include injection site pain, general weakness and elevated liver enzymes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am postmenopausal.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer has grown or come back, shown by scans.

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My breast cancer is HR+ and HER2-, and it has spread.

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I can swallow pills.

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I am currently being treated with a CDK4/6 inhibitor and aromatase inhibitor for advanced breast cancer.

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Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have undergone multiple treatments for my advanced or metastatic disease.

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I have previously been treated with specific hormone or targeted therapies for my cancer.

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I have brain metastases that are causing symptoms or have not been treated.

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I have had chemotherapy for breast cancer that has spread.

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My cancer has spread to my internal organs, lymph system, or brain/spinal cord linings.

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Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ randomization until measured progressive disease (up to 22 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~randomization until measured progressive disease (up to 22 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and randomization until measured progressive disease (up to 22 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-Free Survival (PFS)

Secondary study objectives

Objective Response Rate (ORR): Percentage of Participants Who Achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)

Progression Free Survival (PFS) Determined by Blinded Independent Central Review (BICR)

Side effects data

From 2018 Phase 2 trial • 132 Patients • NCT02102490

91%

Diarrhoea

67%

Nausea

48%

Fatigue

45%

Decreased appetite

35%

Vomiting

27%

Anaemia

26%

Abdominal pain

23%

Asthenia

23%

Neutrophil count decreased

21%

Cough

20%

Constipation

20%

Headache

19%

Arthralgia

18%

White blood cell count decreased

18%

Neutropenia

15%

Alopecia

14%

Dry mouth

14%

Platelet count decreased

14%

Weight decreased

14%

Dysgeusia

13%

Dyspnoea

12%

Abdominal pain upper

12%

Back pain

12%

Dizziness

11%

Oedema peripheral

11%

Dyspepsia

11%

Pyrexia

11%

Blood creatinine increased

10%

Pain

Stomatitis

Aspartate aminotransferase increased

Thrombocytopenia

Lacrimation increased

Dehydration

Dry skin

Pruritus

Alanine aminotransferase increased

Flatulence

Upper respiratory tract infection

Urinary tract infection

Hypokalaemia

Chills

Musculoskeletal chest pain

Musculoskeletal pain

Anxiety

Gastrooesophageal reflux disease

Rash

Myalgia

Cellulitis

Pleural effusion

Atypical pneumonia

Gastroenteritis viral

Lung infection

Sepsis

Fall

Hip fracture

Pneumonitis

Pneumothorax

Febrile neutropenia

Respiratory tract infection

Haematotoxicity

Sinus bradycardia

Tachycardia

Large intestinal obstruction

Pancreatic enzyme abnormality

Pancreatitis

Varices oesophageal

Electrocardiogram abnormal

Liver function test abnormal

Renal function test abnormal

Bone pain

Muscular weakness

Acute kidney injury

Pulmonary embolism

Arterial thrombosis

Epilepsy

100%

80%

60%

40%

20%

Study treatment Arm

Abemaciclib

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm A: Abemaciclib plus FulvestrantExperimental Treatment2 Interventions

Abemaciclib 150 milligram (mg) administered orally twice daily (BID) on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500 mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation criteria were met.

Group II: Arm B: Placebo plus FulvestrantActive Control2 Interventions

Placebo administered orally BID on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500 mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation criteria were met.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fulvestrant

2011

Completed Phase 3

~4160

Abemaciclib

2019

Completed Phase 2

~2120

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CDK4/6 inhibitors like Abemaciclib block cyclin-dependent kinases 4 and 6, preventing cancer cells from progressing through the cell cycle and proliferating. Estrogen receptor antagonists like Fulvestrant bind to estrogen receptors, blocking estrogen's effects and inhibiting the growth of hormone receptor-positive breast cancer cells. These targeted therapies are crucial for effectively managing cancer by directly interfering with specific pathways that cancer cells rely on for growth and survival.

[A Case of Palbociclib plus Fulvestrant‒Resistant Metastatic Breast Cancer That Responded to Abemaciclib plus Fulvestrant].Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial.The role of abemaciclib in treatment of advanced breast cancer.