CARE Initiative: Real-world Emulation of the PALOMA-2 Trial

Aetion

Status

Completed

Conditions

Metastatic Breast Cancer

Treatments

Drug: Palbociclib

Drug: Letrozole

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT06607601

DS3-PALOMA2

Details and patient eligibility

About

The goal of this non-interventional study is to emulate the PALOMA-2 randomized controlled trial of palbociclib as first-line therapy in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer using real-world, electronic health record data. The main questions this study aims to answer are:

Do patients with metastatic ER+/HER2- breast cancer treated with palbociclib and letrozole have improved real-world progression-free survival (rwPFS) compared with patients treated with letrozole alone?
How do the results of this non-interventional study compare to those of the PALOMA-2 randomized controlled trial?

Full description

The Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative is a program designed to build an empirical evidence base for the use of real-world data (RWD) in clinical and regulatory decision-making. Using randomized controlled trials (RCT) as a benchmark for causal effect estimates, a series of RCT emulations will be conducted across varying trials, real world data sources, and study design elements to better understand under what conditions non-interventional studies, using data generated during routine clinical care, can provide reliable conclusions about drug effectiveness.

In this study, real-world electronic health record (EHR) data will be used to emulate the Palbociclib: Ongoing Trials in the Management of Breast Cancer (PALOMA-2) efficacy trial of palbociclib as first-line therapy in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.2 Similarly to the PALOMA-2 trial, this study will compare real-world progression-free survival (rwPFS) between patients who initiate palbociclib and letrozole and those initiating letrozole alone.

Enrollment

724 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Breast cancer diagnosis
Histology not indicative of non-adenocarcinoma histologies
Metastatic disease
Estrogen-receptor positive (ER+)
No prior systemic treatment for metastatic breast cancer
Post-menopausal
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 or missing or Karnofsky performance status >=50 or missing
No lab results indicating inadequate organ function, as defined in the PALOMA-2 RCT protocol

Exclusion criteria

Human epidermal growth factor receptor 2 (HER2) positive tumor
Diagnosis of brain, central nervous system, and/or spinal cord metastases
Neoadjuvant or adjuvant treatment with anastrozole or letrozole ≤12 months before metastatic diagnosis
Prior treatment with treatment with ribociclib, abemaciclib, or palbociclib
Treatment with a CYP3A4 inhibitor or inducer or drugs known to prolong the QT interval, as specified in the PALOMA-2 trial protocol, in the 7 days prior to study treatment initiation
Anti-cancer therapy or major cancer-related surgery within 2 weeks before study treatment initiation
Diagnosis of a second primary malignancy within 3 years prior to study treatment initiation
Diagnosis of long or short QT syndrome, Brugada syndrome, QTc prolongation, or Torsade de Pointes
Diagnosis of hypocalcemia, hypokalemia, or hypomagnesemia
Diagnosis of myocardial infarction, angina, ongoing cardiac dysrhythmias, atrial fibrillation, congestive heart failure, cerebral infarction, transient ischemic attack, or pulmonary embolism in the 6 months prior to study treatment initiation
Diagnosis of inflammatory bowel disease chronic diarrhea, or short bowel syndrome
Diagnosis of human immunodeficiency virus infection