Real-world Treatment Patterns and Effectiveness of Palbociclib and AI Therapy

Real-world Treatment Patterns and Effectiveness of Palbociclib in Combination With an Aromatase Inhibitor as Initial Endocrine Based Therapy in Metastatic/Advanced Breast Cancer

A retrospective observational analysis of de-identified Flatiron Health Analytic Database to describe patient characteristics, treatment patterns and effectiveness of Palbociclib + AI as first-line therapy in HR+/HER2- metastatic breast cancer (MBC) in the US clinical practices.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Palbociclib + an aromatase inhibitor; Drug: Palbociclib + Letrozole; Drug: Letrozole

Detailed Description

Utilizing de-identified data derived from the Flatiron Health Analytic Database, the retrospective observational study is to describe patient characteristics, treatment patterns and effectiveness of Palbociclib + AI as first-line therapy in HR+/HER2-MBC in the US real-world clinical practice setting. Patients will be evaluated retrospectively from index therapy date to death, or last visit in the database, whichever comes first. Descriptive and multivariate statistical analyses will be performed.

• Study Type: Observational
• Enrollment (Actual): 813

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10017
      • Pfizer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HR+/HER2- MBC female adult patients treated with Palbociclib + AI or Letrozole alone between February2015 and end of 2018 or data cut-off date

Description

Inclusion Criteria:

1. Female sex
2. At least 18 years old at MBC diagnosis

3. Diagnosis of MBC at any point in patient history

   1. ICD-9 (174.x, 175.x) or ICD-10 (C50.xx) diagnosis of BC
   2. Confirmation of metastatic disease
   3. At least 2 document clinical visits
   4. Evidence of stage IV or recurrent MBC with a metastatic diagnosis date on or after 2011, as confirmed by unstructured clinical documents

4. HR+/HER2-

   1. HR+: ER+ or PR+ test before or up to 60 days after MBC diagnosis
   2. HER2-: any HER2 negative test and the absence of a positive test (IHC positive 3+, FISH positive/amplified, Positive NOS) before or up to 60 days after MBC diagnosis
5. Palbociclib + AI or letrozole as first-line therapy for MBC during the period from February/2015 through August /31/2018 (or 3 months prior to study cut-off date) to allow for a possible minimum follow-up time of 90 days until the study cutoff date. AI was administered within (±) 28 days of Palbociclib index date.

Exclusion Criteria:

1. Evidence of prior treatment with other CDK4/6I (Ribociclib or Abemaciclib), AI (Letrozole, Exemestane, and Anastrazole), Tamoxifen, Raloxifene, Toremifene, or Fulvestrant for MBC
2. First structured activity greater than 90 days after MBC diagnostic date
3. Treatment with a CDK4/6 inhibitor as part of a clinical trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Palbociclib + an aromatase inhibitor; Adult metastatic breast cancer patients who initiated Palbociclib + an aromatase inhibitor as first line therapy between Feb 3, 2015 to 3 months prior to date of data cutoff in the Flatiron Health Analytic Database.	Drug: Palbociclib + an aromatase inhibitor; Palbociclib + an aromatase inhibitor therapy
Palbociclib + Letrozole; Adult metastatic breast cancer patients who initiated Palbociclib +Letrozole as first line therapy between Feb 3, 2015 to 3 months prior to date of data cutoff in the Flatiron Health Analytic Database.	Drug: Palbociclib + Letrozole; Palbociclib + Letrozole therapy
Letrozole; Adult metastatic breast cancer patients who initiated Letrozole as first line therapy between Feb 3, 2015 to 3 months prior to date of data cutoff in the Flatiron Health Analytic Database.	Drug: Letrozole; Letrozole monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-World Progression Free Survival (rwPFS): Using Kaplan-Meier Method	rwPFS was defined as time (in months) from index date to death or disease progression (growth or worsening in the disease concluded by the treating clinician based on radiology, laboratory evidence, pathology, or clinical assessment) or end of record or end of data availability, whichever occurred first. If participants did not die or had disease progression, they were censored at the date of initiation of next line of therapy for participants with two or more lines of therapy or their last visit date for participants with only one line of therapy. Index date was defined as the start date of the first line therapy for Palbociclib + AI. Kaplan-Meier method was used for analysis.	From index date to death or disease progression or end of record/data availability or censored date, whichever occurred first, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS): Using Kaplan-Meier Method	OS was defined as time (in months) from index date to the date of death. Participants who did not die during the period were censored at the time of data cut-off. Index date was defined as the start date of the first line therapy for Palbociclib + AI. Kaplan-Meier method was used for analysis.	From index date to death, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)
Number of Participants With Real World Tumour Response (rwTR)	rwTR was determined based on complete response (CR), partial response (PR), stable disease (SD), progressive disease(PD), indeterminate and not documented. CR was defined as complete resolution of all visible disease. PR was defined as partial reduction in size of visible disease in some or all areas without any areas of increase in visible disease. SD was defined as no change in overall size of visible disease; also included cases where some lesions increased in size and some lesions decreased in size. PD was determined based on growth or worsening in the disease concluded by the treating clinician based on radiology, laboratory evidence, pathology, or clinical assessment. Index date was defined as the start date of the first line therapy for Palbociclib + AI.	From index date to CR/PR/PD/SD pr PD, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)
Response Rate	Response rate was defined as number of participants with complete response or partial response divided by the number of participants with at least one tumor assessment while on the index treatment. Index date was defined as the start date of the first line therapy for Palbociclib + AI. The result of this outcome measure was measured in terms of proportion of participants.	From index date to CR or PR, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)
Real-World Duration of Treatment (rwDOT): Using Kaplan-Meier Method	rwDOT was defined as time (in months) from index treatment initiation to end of the treatment. Index date was defined as the start date of the first line therapy for Palbociclib + AI. Kaplan-Meier method was used for analysis.	From index treatment initiation up to end of treatment, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)
Time From Index Date to Next Line of Anti-Cancer Therapy: Using Kaplan-Meier Method	The time (in months) from index treatment initiation to next line of anti-cancer therapy or death from any cause, whichever occurred first was reported in this outcome measure. Index date was defined as the start date of the first line therapy for Palbociclib + AI. Kaplan-Meier method was used for analysis.	From index treatment initiation up to next line of anti-cancer therapy or death from any cause, whichever occurred first, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)
Time to First Use of Chemotherapy: Using Kaplan-Meier Method	The time (in months) from index treatment initiation to first use of chemotherapy or death from any cause, whichever occurred first was reported in this outcome measure. Index date was defined as the start date of the first line therapy for Palbociclib + AI. Kaplan-Meier method was used for analysis.	From index treatment initiation to first use of chemotherapy or death from any cause, whichever occurred first, maximum up to approximately 43 months (data was retrieved and observed during 9 months of this retrospective study)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Brufsky A, Liu X, Li B, McRoy L, Layman RM. Real-World Effectiveness of Palbociclib Plus Letrozole vs Letrozole Alone for Metastatic Breast Cancer With Lung or Liver Metastases: Flatiron Database Analysis. Front Oncol. 2022 Jul 4;12:865292. doi: 10.3389/fonc.2022.865292. eCollection 2022.
• Patt D, Liu X, Li B, McRoy L, Layman RM, Brufsky A. Real-World Treatment Patterns and Outcomes of Palbociclib Plus an Aromatase Inhibitor for Metastatic Breast Cancer: Flatiron Database Analysis. Clin Breast Cancer. 2022 Aug;22(6):601-610. doi: 10.1016/j.clbc.2022.05.002. Epub 2022 May 5.
• DeMichele A, Cristofanilli M, Brufsky A, Liu X, Mardekian J, McRoy L, Layman RM, Emir B, Torres MA, Rugo HS, Finn RS. Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. Breast Cancer Res. 2021 Mar 24;23(1):37. doi: 10.1186/s13058-021-01409-8.
• Brufsky A, Liu X, Li B, McRoy L, Layman RM. Real-World Tumor Response of Palbociclib Plus Letrozole Versus Letrozole for Metastatic Breast Cancer in US Clinical Practice. Target Oncol. 2021 Sep;16(5):601-611. doi: 10.1007/s11523-021-00826-1. Epub 2021 Aug 2. Erratum In: Target Oncol. 2021 Nov;16(6):865. doi: 10.1007/s11523-021-00847-w.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2019
• Primary Completion (Actual): September 27, 2019
• Study Completion (Actual): September 27, 2019

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; Effectiveness; Palbociclib; Real-world data; Retrospective study
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Palbociclib; Aromatase Inhibitors
• Other Study ID Numbers: A5481122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No