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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Palbocicilib; Drug: Ribociclib; Drug: Abemaciclib

Detailed Description

Breast cancer (BC) is the most common type of cancer in women worldwide and accounted for 684,996 BC-associated deaths in 2020. BC was ranked as the highest incident cancer in Middle Eastern countries, accounting for approximately 17.7% to 19% of all new diagnoses of cancers in 2018. BC can be classified into different categories based on different schemes. The classification is primarily based on the histopathological type, the grade of the tumor, the stage of the tumor, and the protein and gene expression status. To improve patient care, the National Comprehensive Cancer Network (NCCN) has outlined treatment and monitoring guidelines for BC. These guidelines recommend an initial course of endocrine therapy (ET), such as a selective estrogen receptor modulator (SERM) (e.g., tamoxifen), with or without ovarian ablation/suppression in premenopausal women with HR+ aBC. Chemotherapy is recommended only when there is clear evidence of resistance to ET or in the case of an immediately life-threatening disease. There are some data available that can provide some insights about the incidence of BC among Egyptian women. The basic incidence rates on the national level without non-melanoma skin cancer were 113.1/100,000 (both genders), 115.7/100,000 (males), and 110.3/100,000 (females). The National Cancer Registry Program (NCRP) was developed in 2008 and came to be the sole foundation for cancer prevalence in Egypt. Cyclin-dependent kinase 4/6 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.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt
      • Gustave Roussy International Hospital in Egypt.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• Inclusion criteria

  • Eligible patients will be who with histologically confirmed invasive breast carcinoma with HR positive and HER2 negative phenotype and clinical or radiological evidence of metastasis.
  • Only patients with complete medical records from January 2020 December 2024 will be included.

• Exclusion criteria

  • Exclusion criteria will be devised to ensure the collection of authentic real world data excluding patients those with insufficient clinical documentation, unknown clinical outcomes, or those who transferred to another treatment center during their therapy course.
  • Females younger than 18 years will be excluded.
  • Patients in visceral crisis .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group 1: ETH + palbciclib; in this group patient receive endocrine therapy (ETH) + Palbociclib as active comparator	Drug: Palbocicilib; 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; Other Names: Ibrance
Active Comparator: group 2 : ETH + Ribociclib; Patients in this group receive endocrine therapy (ETH) + Ribociclib as active comparator	Drug: Ribociclib; Ribociclib administered according to standard dosing regimen (600 mg / day ) for 3 consecutive weeks , one week off per month; Other Names: Kasqali
Active Comparator: group 3 : ETH + Abemaciclib; Patients in this group receive endocrine therapy (ETH) + Abemaciclib as active comparator.	Drug: Abemaciclib; Abemaciclib administered according to standard dosing regimen (300 mg / day ) for 3 consecutive weeks , one week off per month; Other Names: Versinio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1- Progression free survival (PFS).	Time from treatment initiation to disease progression or death, measured in months.	1 year
2-Overall Survival	Time from treatment initiation to death from any cause, measured in months.	1 year
Incidence of Treatment-Related Adverse Events	Frequency and severity of adverse events assessed using CTCAE v4.0.	1 year
Economic outcomes	Economic outcomes will be assess cost-utility analysis and the results will be expressed in terms of " Incremental-cost-effectiveness ratio (ICER) ".	1 year

Collaborators and Investigators

• Sponsor: Beni-Suef University

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2024
• Primary Completion (Actual): October 20, 2025
• Study Completion (Actual): December 20, 2025

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer , CDK4/6 Inhibitors , Pharmacoeconomics
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; abemaciclib; ribociclib; palbociclib
• Other Study ID Numbers: 7-2025/5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No