care initiative: real-world emulation of the paloma-2 trial

Conditions: Metastatic Breast Cancer

Summary: 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: 1. 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? 2. how do the results of this non-interventional study compare to those of the paloma-2 randomized controlled trial?

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.

Eligibility criteria:
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 \&gt;=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

Keywords: real-world evidence real-world data oncology pharmacoepidemiology comparative effectiveness research trial emulation