Emulation of the MONALEESA-2 Trial Using Specialty Oncology Electronic Health Records Databases

Randomized controlled trials (RCTs) are generally regarded as the gold-standard of evidence for establishing efficacy of medical products. However, real-world data (RWD) are increasingly used to complement evidence from RCTs. Yet, to have confidence in the accuracy of non-interventional studies medical products and their outcomes in oncology, investigators need to know what questions can be validly answered, with which non-interventional study designs, and which analysis methods are appropriate, given the data that is available. Building on a process from the RCT DUPLICATE initiative1-4 EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) is part of the expansion project specific to oncology and aims to emulate 12 randomized oncology RCTs using multiple EHR data sources.

The purpose of this protocol is to describe the emulation of the MONALEESA-2 trial. MONALEESA-2 was a Phase III, double-blind, randomized study assessing the efficacy and safety of ribociclib (600 mg orally once daily on days 1-21 of a 28-day cycle, followed by 7 days off) in combination with letrozole (2.5 mg orally once daily, continuously) versus letrozole alone in postmenopausal women with hormone receptor-positive [estrogen receptor (ER) and/or progesterone receptor (PR)], human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who had not received prior systemic treatment for their advanced disease.

Study Period:

ENCORE database 1 (EDB1): Patient identification period: 01/01/2011-04/30/2024 with follow-up information through data cut-off date on 04/30/2024 ENCORE database 3 (EDB3): Follow-up information through June 2023 (there is no specific time period restrictions for patient eligibility) ENCORE database 4 (EDB4): Patient identification period: 10/01/2018-09/30/2023 with follow-up information through data cut-off date on 09/30/2023.

Inclusion criteria

• Age ≥18 years through 2017 to 2023
• Metastatic breast cancer
• Hormone receptor positive (ER/PR+)
• Untreated with systemic anticancer therapy for advanced disease
• ECOG performance status of 0 or 1
• HER2-negative

Exclusion criteria

• Prior treatment with CDK4/6 inhibitor
• Locally advanced (unresectable) or inflammatory breast cancer
• Non-breast cancer malignancy other than basal/squamous cell skin cancer or carcinoma in situ of cervix
• Prior adjuvant therapy for breast cancer
• Systemic anticancer therapy other than ribociclib or letrozole