Real-World Effectiveness of Palbociclib in Combination With an Aromatase Inhibitor

Real-World Treatment Effectiveness of Palbociclib in Combination With an Aromatase Inhibitor as 1st Line Therapy in Metastatic Breast Cancer

A retrospective study of de-identified (to preserve patient privacy) patient information from the Flatiron Health Analytic Database to compare effectiveness (i.e., overall survival) of first line palbociclib + aromatase inhibitor (AI) versus AI alone treatment in postmenopausal women or men with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (MBC) in the United States clinical practices.

Study Overview

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

• Study Type: Observational
• Enrollment (Actual): 2888

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HR+/HER2- MBC adult patients treated with Palbociclib + AI or AI alone between February2015 and September, 2020

Description

Inclusion Criteria:

• Confirmed HR+/HER2- status after MBC diagnosis.
• Received palbociclib + AI or AI as first-line therapy

Exclusion Criteria:

• Evidence of prior treatment with other CDK4/6I, AI, tamoxifen, raloxifene, toremifene, or Fulvestrant for MBC
• First structured activity greater than 90 days after MBC diagnostic date
• Treatment with a CDK4/6 inhibitor as part of a clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

2

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 March 31, 2020 in the Flatiron Health Analytic Database.	Drug: Palbociclib + an aromatase inhibitor; Palbociclib + an aromatase inhibitor therapy
Aromatase inhibitor; Adult metastatic breast cancer patients who initiated an aromatase inhibitor as first line therapy between Feb 3, 2015 to March 31, 2020 in the Flatiron Health Analytic Database.	Drug: Aromatase inhibitor; Aromatase inhibitor therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Postmenopausal Female or Male Participants With Metastatic Breast Cancer	OS was defined as the time from the index date (start of palbociclib + AI or AI alone) to death. Participants who did not die, were censored at the end of study date (30-Sep-2020). Kaplan-Meier method adjusted by stabilized inverse probability of treatment weighting (sIPTW) was used.	From index date to death due to any cause or censoring date of 30-Sep-2020 (approximately up to 68 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-World Progression Free Survival (rwPFS) in Postmenopausal Female or in Male Participants With Metastatic Breast Cancer	Real-world PFS was defined as the number of months from start of palbociclib + AI or AI alone to death from any cause or disease progression (based on clinical assessment or by radiographic scan/tissue biopsy), whichever occurred first. Disease progression was defined as at least a 20 percentage (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that was the smallest on study). Participants who did not die and did not have disease progression were censored at the date of initiation of next line of therapy for participants with 2 or more lines of therapy or at the date of their last visit during the study period (February 2015-September 2020) for participants with only 1 line of therapy. Kaplan-Meier method adjusted by stabilized IPTW was used.	From index date until disease progression or death due to any cause or censoring date (approximately up to 68 months)
Number of Participants According to Real-World Tumor Responses (rwTR): Postmenopausal Female or in Male Participants With Metastatic Breast Cancer	Real-world best responses were assessed based on treating clinician's assessment of radiological evidence for change in burden of disease over course of treatment after 1 month of index treatment initiation. Responses were classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), indeterminate response (IR). CR=Complete resolution of all visible disease. PR=partial reduction in size of visible disease in some or all areas without any areas of increase in visible disease. SD=no change in overall size of visible disease. PD: an increase in visible disease; also included cases where some lesions increased in size and some lesions decreased in size; included cases where clinician indicated progressive disease; IR=study data not available for evaluation of efficacy for any reason, including participants lost to follow-up or assessment not undertaken or death. Analysis was performed using sIPTW method to balance participant characteristics.	From 30 days after index treatment initiation until CR, PR, SD or PD (approximately 67 months)
Real-World Response Rate (rwTR) in Postmenopausal Female or in Male Participants With Metastatic Breast Cancer	Real-world tumor response rate (rwTR) was defined as the percentage of participants with a real world complete response (rwCR) or real-world partial response (rwPR). CR: complete resolution of all visible disease. PR: partial reduction in size of visible disease in some or all areas without any areas of increase in visible disease. Analysis was performed using sIPTW method to balance participant characteristics.	From 30 days after index treatment initiation until disease progression or death due to any cause or censoring date (approximately up to 67 months)
Number of Participants According to Initial Dose of Palbociclib: Palbociclib + Aromatase Inhibitor Arm Only	Number of participants according to the initial dose of palbociclib (75 milligrams [mg]/day, 100mg/day, 125 mg/day or missing dose) are reported in this outcome measure.	At index (anytime between 03-Feb-2015 to 31-Mar-2020, approximately up to 62 months)
Time to Dose Adjustment for Palbociclib- Palbociclib + Aromatase Inhibitor Arm Only	Time to dose adjustment for participants who received palbociclib 125 mg/day, 100 mg/day, or 75 mg/day as initial dose was presented in this outcome measure.	At index (anytime between 03-Feb-2015 to 30-Sep-2020, approximately up to 68 months)
Duration of Treatment	Duration of treatment was defined as days from index prescription order date to end of treatment, start of subsequent line of therapy, or death from any cause, whichever occurred first. Kaplan-Meier method adjusted by stabilized IPTW was used.	From start of study treatment to end of treatment, start of subsequent line of therapy, or death from any cause, whichever occurred first (up to 68 months)
Time to Next Line of Treatment	Time to next line of treatment represents the interval from commencement of one treatment to initiation of the next line of therapy. Analysis was performed using sIPTW method to balance participant characteristics among reporting groups.	From start of study treatment to start of next line of therapy (up to 68 months)
Time to Subsequent Chemotherapy	Time to subsequent chemotherapy represents the time interval to administration of a different chemotherapeutic agent after the first course of therapy was administered. Analysis was performed using sIPTW method to balance participant characteristics among reporting groups.	From start of study treatment to administration of different chemotherapeutic agent (up to 68 months)
Real-World Progression Free Survival 2 (rwPFS2) in Postmenopausal Female or in Male Participants With Metastatic Breast Cancer	rwPFS2 was defined as the time from the index date to the date of the first documentation of a rwPD or death due to any cause after starting second line of therapy, whichever occurs first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Analysis was performed using sIPTW method to balance participant characteristics among reporting groups.	From start of study treatment until disease progression, or death from any cause following second line of therapy, whichever occurred first (approximately up to 68 months)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Rugo HS, Brufsky A, Liu X, Li B, McRoy L, Chen C, Layman RM, Cristofanilli M, Torres MA, Curigliano G, Finn RS, DeMichele A. Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer. NPJ Breast Cancer. 2022 Oct 11;8(1):114. doi: 10.1038/s41523-022-00479-x.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: cyclin-dependent kinase 4/6i (CDK4/6i)
• 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; Palbociclib; Aromatase Inhibitors
• Other Study ID Numbers: A5481151

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.