Clinical trial NCT06607601: CARE Initiative: Real-world Emulation of the PALOMA-2 Trial
Official title: CARE Initiative Study: Real-world Emulation of the PALOMA-2 Comparative Effectiveness Trial of Palbociclib and Letrozole vs. Placebo and Letrozole for the First-line Treatment of ER+/HER2- Advanced Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Breast Cancer
Keywords: real-world evidence
real-world data
oncology
pharmacoepidemiology
comparative effectiveness research
trial emulation
Lead sponsor: Aetion, Inc.
Sponsor class: OTHER
Collaborators: name: AbbVie
name: Amgen
name: AstraZeneca
name: Bayer
name: Gilead Sciences
name: Janssen, LP
name: Pfizer
First posted: 2024-09-23
Enrollment: 724
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients identified in the electronic health record data source with metastatic ER+/HER2- breast cancer initiating treatment with the study drugs (palbociclib, letrozole)

Brief 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?

Detailed 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.

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

Primary outcomes:
measure: Real-world progression-free survival (rwPFS)
timeFrame: From study treatment initiation until the date of disease progression, death from any cause or censoring, whichever came first, assessed up to 33 months.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Dieras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. doi: 10.1056/NEJMoa1607303.