Clinical and Pharmacoeconomic Assessment of CDK4/6 Inhibitors for Treatment of Breast Cancer in Egypt

Sponsor
Beni-Suef University
Study ID
NCT07487129
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Palbocicilib — DRUG
    Patient receive standard endocrine therapy (ETH) in combination with Palbociclib. palbociclib administered according to standard dosing regimen (125mg /day ) for 3 consecutive weeks , one week off per month
  • Ribociclib — DRUG
    Ribociclib administered according to standard dosing regimen (600 mg / day ) for 3 consecutive weeks , one week off per month
  • Abemaciclib — DRUG
    Abemaciclib administered according to standard dosing regimen (300 mg / day ) for 3 consecutive weeks , one week off per month

Study Details

Cyclin-dependent kinases CDK4/6 inhibitors (CDK4/6i) combined with ET are considered the standard of care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced BC (HR+/HER2-ABC). CDK4/6 inhibitors are the first ones that were approved by the FDA for clinical treatment. These inhibitors specifically inhibit CDK4/6 and show limited toxicity to normal cells. There are three FDA-approved CDK4/6 inhibitors, and they are palbociclib produced by Pfizer, ribociclib produced by Novartis, and abemaciclib produced by Eli Lilly. Palbociclib is the first and most popular CDK4/6 inhibitor, which reached $2.135 billion in global sales in 2016. Ribociclib is very similar to palbociclib in structure, but abemaciclib is quite different. In vitro studies indicated that palbociclib has an almost equivalent inhibition effect on CDK4 and CDK6, while abemaciclib and ribociclib are more potent against CDK4 than CDK6. CDKs are protein kinases that phosphorylate cellular proteins, causing their activation or inactivation during the G1 cell cycle phase. In a dysregulated cell cycle, CDK4/6 proteins bind to cyclin D1 to form an activated complex, which then phosphorylates and inactivates tumor suppressor retinoblastoma protein and releases E2F transcription factors, thus resulting in cell cycle progression and cancer cell proliferation. Introducing highly selective inhibitors of this pathway into clinical practice as CDK4/6 inhibitors (CDKi), which act by blocking the cyclin D1/CDK4/6 complex and inhibit cell cycle progression to the S phase and cancer proliferation, is very promising. These novel molecular mechanisms provide a theoretical basis for combination therapy with CDK4/6 inhibitors. For instance, CDK4/6 inhibitors combined with the hormone receptor antagonist letrozole have been applied for BC therapy. Many other combination therapies involving CDK4/6 inhibitors are currently under clinical trials for a variety of diseases, including anti-cancer therapy. Moreover, the addition of CDKi to ET has been associated with significant improvement in progression-free survival (PFS) and/or overall survival (OS) in hormone receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Despite the clear clinical benefit from the addition of CDKi to ET shown in several clinical trials, it is critical to assess the efficacy and safety of the combination treatment in routine clinical practice. Real-world data are often used to assess drug efficacy, tolerability, and cost to demonstrate the reproducibility of evidence from randomized clinical trials in daily clinical practice. In addition, real-world data (RWD) enable the assessment of clinical benefit and safety of regimens in populations that are often excluded from clinical trials, such as elderly patients, patients with poor performance status, or patients with multiple comorbidities. Ribociclib (RIB) + ET demonstrated statistically significant PFS and OS benefits over ET alone in 3 Phase 3 clinical trials (MONALEESA-2, -3, and -7) in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) ABC, including patients with visceral metastases and a high tumor burden. Pharmacoeconomics is a subdiscipline of health economics that is concerned with the comparison and analysis of costs to the related consequences of drug therapy options and strategies. Pharmacoeconomics is specifically important due to the increasing drug therapeutic options and their costs, which are estimated to account for at least 10% of the total health expenditures of each country.

Key Dates

Start date
Aug 25, 2024
Status verified
Mar 2026
Primary completion
Oct 20, 2025
Completion
Dec 20, 2025

Study Design

Enrollment
206 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: group 1: ETH + palbciclib
    in this group patient receive endocrine therapy (ETH) + Palbociclib as active comparator
  • Active Comparator: group 2 : ETH + Ribociclib
    Patients in this group receive endocrine therapy (ETH) + Ribociclib as active comparator
  • Active Comparator: group 3 : ETH + Abemaciclib
    Patients in this group receive endocrine therapy (ETH) + Abemaciclib as active comparator.

Primary Outcome Measure

1- Progression free survival (PFS). [ Time Frame: 1 year ]

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