Advanced Breast Cancer
Conditions
Brief summary
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
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 initiative. EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) is the trial emulation discussed in this protocol 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 PALOMA-2 trial. PALOMA-2 was a Phase III, double-blind, randomized study assessing the efficacy and safety of palbociclib (125 mg orally, once daily for 21 days of a 28-day cycle) in combination with letrozole (2.5 mg orally, once daily, continuously) versus letrozole alone in postmenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who had not received prior systemic treatment for their advanced disease.
Interventions
DRUGInitiation of palbociclib plus letrozole
Initiation of palbociclib plus letrozole described in electronic health records is used as the exposure.
Initiation of letrozole described in electronic health records is used as the reference.
Sponsors
Brigham and Women's Hospital
Food and Drug Administration (FDA)
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 * Postmenopausal women with ER-positive, HER2-negative locally advanced or metastatic breast cancer who receive treatment without curative intent * The line of therapy for patients in EDB1 and EDB3 is implicitly advanced/metastatic because the line of therapy classification starts after their advanced/metastatic diagnosis in the respective database * In EDB4, patients must explicitly have any evidence of a metastasis prior initiating palbociclib plus letrozole or letrozole alone * Adenocarcinoma histology * No prior systemic treatment for advanced/metastatic disease * ECOG performance status of 0 or 1
Exclusion criteria
* HER2+ * CNS metastases * Prior treatment with CDK4/6 inhibitor * Non-breast cancer malignancy other than basal/squamous cell skin cancer or carcinoma in situ of cervix * Systemic anticancer therapy other than palbocicilib or letrozole * Treatment with non-steroidal aromatase inhibitor (i.e.anastrozole, letrozole)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to all-cause mortality (overall survival) | Through the earliest of outcome, censoring, or end of data (April 2024) | Hazard ratio (95% CI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to next treatment (TTNT) | Through the earliest of outcome, censoring, or end of data (April 2024) | Median overall survival time (difference) in % (95% CI) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShirley Wang, PhD, ScM
Brigham and Women's Hospital
PRINCIPAL_INVESTIGATORDenys Shay, MD
Brigham and Women's Hospital
Outcome results
None listed