Patterns of Treatment and Outcome of Palbociclib Plus Endocrine Therapy

Patterns of Treatment and Outcome of Palbociclib Plus Endocrine Therapy in Hormone Receptor-positive (HR+)/HER2 Receptor-negative (HER2-) Metastatic Breast Cancer (MBC): a Real World Multicentre Italian Study

This is a multicentre real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary endpoint is the clinical benefit rate (CBR); secondary aims are the median PFS (mPFS), overall survival (OS) and safety.

Study Overview

• Status: Completed
• Conditions: Female; Neoplasm Malignant; Breast
• Intervention / Treatment: Drug: Palbociclib; Drug: Letrozole 2.5mg; Drug: Fulvestrant

Detailed Description

This is an open-label, longitudinal, prospective, multicentre cohort study. Eligible patients are pre- and postmenopausal women with a histologically proven HR+ MBC, candidate to receive palbociclib plus endocrine therapy (ET) as first or subsequent line of therapy according to their contingent clinical situation. Additional inclusion criteria are HER2- disease (immunohistochemistry (IHC) 0-1+ or IHC 2+, confirmed as fluorescence in situ hybridization [FISH] negative), presence of measurable or evaluable lesions and life expectancy of at least 4 months. They need to have adequate bone marrow, hepatic and renal function, according to clinical practice guidelines for antineoplastic drug administration. Previous chemotherapy or ET for metastatic disease is allowed. Patients receive palbociclib 125 mg daily, 3 weeks on/1 week off in a 28-day cycle, combined with letrozole 2.5 mg administered orally on a continuous daily dosing schedule (cohort A) or fulvestrant at the dose of 500 mg intramuscular on days 1, 14, 28, then every 4 weeks thereafter (cohort B). Premenopausal women receive a GnRH analogue in combination with ET and palbociclib. Treatment is administered until documented disease progression (PD), unacceptable toxicity or patient refusal. The tumour assessment is performed approximately every 16 weeks. Treatment efficacy is evaluated by Response Evaluation Criteria In Solid Tumors (RECIST version 1.1). A complete blood count and organ function test is performed before each cycle, through study completion, an avarange of 1 year. No pre-specified treatment modifications are planned; dose reductions, delay or discontinuations of palbociclib are performed according to observed side effects. AEs are recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0).

The primary aim of the study is to analyse the activity of palbociclib plus ET in terms of clinical benefit rate that is defined as the percentage of patients experiencing complete response (CR), partial response (PR), or stable disease (SD) lasting 6 months or more. Secondary aims include the evaluation of the safety of the treatments, progression-free survival and overall survival.

• Study Type: Observational
• Enrollment (Actual): 191

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Istituti Clinici Scientifici Maugeri IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

One hundred-ninety-one patients (92 in cohort A, 99 in cohort B) were enrolled and treated and 182 were evaluable for the analysis. Median age was 62 years (range 47-79)

Description

Inclusion Criteria:

• Pre- and postmenopausal women with a histologically proven HR+MBC, candidate to receive palbociclib plus ET as first or subsequent line of therapy according to their contingent clinical situation.
• HER2- disease (IHC 0-1 or IHC 2, confirmed as FISH negative), presence of measurable or evaluable lesions and life expectancy of at least 4 months.
• Adequate bone marrow, hepatic and renal function, according to clinical practice guidelines for antineoplastic drug administration

Exclusion Criteria:

• ER- PgR- disease
• HER2+ disease (IHC 3 or IHC 2, confirmed as FISH positive)
• Any cardiovascular, renal or hepatic condition that would compromise conditions in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; Patients that received palbociclib combined with letrozole 2.5 mg	Drug: Palbociclib; tablets; Other Names: ibrance; Drug: Letrozole 2.5mg; tablets; Other Names: Femara
Cohort B; Patients that received palbociclib combined with fulvestrant 500 mg	Drug: Palbociclib; tablets; Other Names: ibrance; Drug: Fulvestrant; intramuscolar injections; Other Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR)	the percentage of patients experiencing complete response (CR), partial response (PR), or stable disease (SD) lasting 6 months or more	From the date of randomization through study completion, assessed up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median PFS	the time interval from the start of therapy with palbociclib plus ET to the date of	From date of randomization until the date of first documented progression, assessed up to 16 weeks through study completion
Overall survival	the interval from therapy start to the date of death or of last follow-up evaluation	from the date of randomization until the date of death from any cause or lost of follow-up, whichever came first, assessed up to 100 months.
Drug safety and tolerability	Incidence of Treatment-emergent adverse events (safety and tolerability) using CTCAE criteria	at day 1 of any cycle from the date of the start of therapy through study completion, an avarange of 1 year

Collaborators and Investigators

• Sponsor: Istituti Clinici Scientifici Maugeri SpA
• Investigators: Principal Investigator: Raffaella Palumbo, MD, PhD, ICS Maugeri, IRCCS, Department of Medical Oncology, Pavia, italy

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: metastatic breast cancer; palbociclib; endocrine therapy; real world; visceral involvement
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Letrozole; Fulvestrant; Palbociclib
• Other Study ID Numbers: CE 2295

Drug and device information, study documents

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