letrozole and Neutropenia

letrozole has been researched along with Neutropenia in 15 studies

Neutropenia: A decrease in the number of NEUTROPHILS found in the blood.

Research

Studies (15)

Authors

Clinical Trials (14)

Trial Overview

Trial Outcomes

Clinical Benefit Rate (CBR) Based on Investigator's Assessment (Core Phase)

"Clinical benefit rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment.~CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.~SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.~95% CI was calculated using the exact binomial method." (NCT02941926)
Timeframe: Up to approximately 33 months

Overall Response Rate (ORR) Based on Investigator's Assessment (Core Phase)

"Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment.~CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.~95% CI was calculated using the exact binomial method." (NCT02941926)
Timeframe: Up to approximately 33 months

Time-to-Progression (TTP) Based on Investigator's Assessment (Core Phase)

"Time to progression (TTP) is defined as time from date of start of treatment to the date of first documented progression or death due to underlying cancer. Participants with symptoms of rapidly progressing disease without radiologic evidence were classified as progression only when clear evidence of clinical deterioration was documented and/or patient discontinued due to 'Disease progression' or death due to study indication. When there was no documentation of radiologic evidence of progression, and the patient discontinued for 'Disease progression' due to documented clinical deterioration of disease, the date of discontinuation was used as date of progression.~TTP was estimated using the Kaplan-Meier method. 95% CI of median was calculated according to Brookmeyer and Crowley method." (NCT02941926)
Timeframe: Up to approximately 33 months

All Collected Deaths

"On-treatment- Core phase: from first treatment in the Core phase up to 30 days post-treatment (for participants who did not enter the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase). Extension phase: from first dose of treatment in the Extension phase up to 30 days after last dose of treatment.~Post-treatment survival follow-up- Core phase: from 31 days post-treatment in the core phase up to end of study; Extension phase: from 31 days post-treatment in the Extension phase up to end of study." (NCT02941926)
Timeframe: On-treatment Core Phase: up to 33 months; Post-treatment survival Follow-up Core Phase: Up to 33 months; On-treatment Extension Phase: up to approximately 37.6 months; Post-treatment survival Follow-up Extension Phase: Up to approximately 37.6 months.

Canadian Sub-study: Proteomic Analysis of Ribociclib and Letrozole Cohort Not Achieving Clinical Benefit Compared to a Cohort Sensitive to Treatment With Ribociclib and Letrozole

Exploratory analysis performed in archival tumor samples collected during screening in the main study. Protein expression levels of the ribociclib plus letrozole cohort that did not achieve clinical benefit (progression within 3 months of treatment) and the cohort sensitive to ribociclib and letrozole (cohort with a time to progression of 22 months or more) were determined using using Single-Pot, Solid-Phase-enhanced, Sample Preparation-Clinical Tissue Proteomics (SP3-CTP). For normalization purposes a pooled internal standard sample, comprised of aliquots of every sample included in the study, was included in each experimental batch. Protein abundances were calculated as the log2 transformed abundances relative to the pooled internal standard. Positive values represent higher protein expression levels compared to the pooled internal standard. Expression levels of proteins that showed association to predicting response to study treatment are presented. (NCT02941926)
Timeframe: Screening (up to 28 days before first dose of study treatment)

Change From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Score (Core Phase)

"Change from baseline in FACT-B scores was assessed. FACT-B is a self-report instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL.~Due to the nature of the questionnaire, only females were asked to complete this questionnaire." (NCT02941926)
Timeframe: On Day 1 of Cycle 1, 2, 3, 4 ,5, 6, 8, 10, 12 and after that every 3 cycles, and End of treatment, assessed up to 33 months. Cycle=28 days

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment With Ribociclib + Letrozole in the Core Phase

"AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s).~SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. A SAE which caused death of the participant was considered as fatal SAE.~AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE.~A participant with multiple severity grades for an AE is only counted under the maximum grade." (NCT02941926)
Timeframe: From start of treatment up to 30 days after last treatment (for participants who did not enter to the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase), assessed up to approximately 33 months.

Number of Participants With AEs and SAEs in the Extension Phase

"AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s).~SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization.~AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE.~A participant with multiple severity grades for an AE is only counted under the maximum grade." (NCT02941926)
Timeframe: From first dose of treatment in the Extension phase up to 30 days after last dose of treatment, assessed up approximately 37.6 months

Number of Participants With Clinical Benefit (Extension Phase)

Clinical benefit as assessed by the Investigator during Extension phase (NCT02941926)
Timeframe: On Day 1 of every 3 cycles, starting from Cycle 1 of the Extension phase until end of treatment, assessed up to 37.4 months. Cycle= 28 days

Overall Response Rate (ORR) as Per Investigator Assessment

Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. (NCT01958021)
Timeframe: Up to approximately 20 months

Progression Free Survival (PFS) Per Investigator Assessment

PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1 (NCT01958021)
Timeframe: Up to approximately 20 months

Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) (Participants With Objective Disease Response)

DOR was defined as the time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. DOR data was censored on the date of the last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, DOR was based on BICR. (NCT02297438)
Timeframe: Randomization up to 65 months

Duration of Response (DOR) Based on Investigator Assessment (Participants With Objective Disease Response)

DOR was defined as the time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. DOR data was censored on the date of the last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, DOR was based on investigator assessment. (NCT02297438)
Timeframe: Randomization up to 65 months

Median Baseline Percent (%) Positive Cells for Ki67

Archived formalin-fixed paraffin embedded (FFPE) specimen from the original diagnostic tumor tissue was collected and sent to the sponsor-designated central laboratories for assessment of Ki67 associated with sensitivity and/or resistance to Palbociclib. (NCT02297438)
Timeframe: Baseline

Overall Survival (OS)

OS was defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was assessed using Kaplan-Meier methods. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants Wiht Objective Response (OR) Based on Investigator Assessment

OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on investigator assessment. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR)

DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on BICR. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)

DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on BICR. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment

DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on investigator assessment. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)

DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on investigator assessment. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR)

OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on BICR. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)

OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on BICR. (NCT02297438)
Timeframe: Randomization up to 65 months

Percentage of Participants With Objective Response (OR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)

OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on investigator assessment. (NCT02297438)
Timeframe: Randomization up to 65 months

Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR)

PFS was based on Kaplan-Meier estimates. PFS was defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause in the absence of documented progressive disease, whichever occurs first. In this outcome measure, PFS was based on BICR. (NCT02297438)
Timeframe: Randomization up to 65 months

Progression-Free Survival (PFS) Based on Investigator's Assessment

PFS was based on Kaplan-Meier estimates. PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. In this outcome measure, PFS was based on investigator's assessment. (NCT02297438)
Timeframe: Randomization up to 65 months

1-Year, 2-Year and 3-Year Survival Probability

OS was defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. The 1-year survival probability was estimated using the Kaplan-Meier method and a 2-sided 95% confidence interval (CI) for the log [-log(1 year survival probability)] was be calculated using a normal approximation, and then back transformed to give a CI for the 1-year survival probability itself. The 2-year, and 3-year survival probabilities were estimated similarly. (NCT02297438)
Timeframe: Randomization up to 65 months

Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores

The EQ VAS recorded the participant's self rated questionnaire to assess generic health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). Published weights were available that allow for the creation of a single summary score. (NCT02297438)
Timeframe: Baseline up to Cycle 65 Day 1

Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores

The EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/depression); a participant was asked to rate each state on a 3 level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. (NCT02297438)
Timeframe: Baseline up to Cycle 65 Day 1

Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score

"The Functional Assessment of Cancer Therapy (FACT) is a modular approach to assess participant health related quality of life using a core set of questions (FACT-G) as well as a cancer site specific module. The FACT-G was a 27-item compilation of general questions divided into 4 domains: Physical Well Being, Social/Family Well Being, Emotional Well Being, and Functional Well Being. The FACT-B consists of the FACT-G (27 items) and a breast specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a 5-level scale ranging from 0=Not at all to 4=Very much. FACT-B total score = FACT-G + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-148, with 0 being the worst possible score and 148 the best. A positive change of the total score indicated improvement from baseline and a negative change indicated deterioration." (NCT02297438)
Timeframe: Baseline up to Cycle 65 Day 1

Number of Participants With Detection in Estrogen Receptor (ER)

Archived formalin-fixed paraffin embedded (FFPE) specimen from the original diagnostic tumor tissue was collected and sent to the sponsor-designated central laboratories for assessment of ER associated with sensitivity and/or resistance to Palbociclib. (NCT02297438)
Timeframe: Baseline

Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology

The laboratory results were graded according to the National Cancer Institute (NCI) CTCAE v4.0 severity grade. Shift tables were provided to examine the distribution of laboratory toxicities. The following hematology parameters had met the criteria of CTCAE grade shift change from Grade <=2 at baseline to Grade 3 or 4 post baseline: neutrophils (absolute), white blood cells, platelets, anemia and hemoglobin increased. (NCT02297438)
Timeframe: Randomization up to 65 months

Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry

The laboratory results were graded according to the National Cancer Institute (NCI) CTCAE v4.0 severity grade. Shift tables were provided to examine the distribution of laboratory toxicities. The following chemistry parameters had met the criteria of CTCAE grade shift change from Grade <=2 at baseline to Grade 3 or 4 post baseline: alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia. (NCT02297438)
Timeframe: Randomization up to 65 months

Number of Participants With Treatment-Emergent Adverse Events (All Causalities)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Participants were counted only once per treatment in each row. (NCT02297438)
Timeframe: Randomization up to 65 months

Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by the investigator (Yes/No). Participants were counted only once per treatment in each row. (NCT02297438)
Timeframe: Randomization up to 65 months

Trough Plasma Concentration of Palbociclib

Summary of palbociclib trough concentrations (NCT02297438)
Timeframe: Pre-dose on Day 14 of Cycle 1 and Cycle 2

Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index

The EuroQol EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It contains 5 descriptors of current health state (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 3 levels of function (1=no problem, 2=some problem, and 3=extreme problem). The scores on the 5 descriptors are summarized to create a single summary score. An overall utility score is calculated based on these domains, with a range score from 0 (worse health scenario) to a maximum of 1.0 (best health scenario). (NCT01740427)
Timeframe: From Baseline up to 2.5 years

Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy -Breast (FACT-B)

FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The FACT-B consisted of the FACT-G (27-item) and a breast-specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. FACT-B total score = Physical Well-Being + Social/Family Well-Being + Emotional Well-Being + Functional Well-Being + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-144, with 0 being the worst possible score and 144 the best. (NCT01740427)
Timeframe: From Baseline up to 2.5 years

Disease Control (DC)/Clinical Benefit Response (CBR)

DC is defined as the overall CR, PR, or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Disease Control Rate (DCR) is defined as the patients with CR, PR, or SD ≥24 weeks relative to all randomized participants. Participants who do not have on-study radiographic tumor reevaluation, who received anti-tumor treatment, a best response of SD≥24 weeks, or who died, progressed,or dropped out for any reason prior to achieving reaching a CR or PR and a best response of SD≥24 weeks was counted as non-responders in DCR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. SD: neither sufficient shrinkage nor increase to qualify for disease progression (NCT01740427)
Timeframe: From randomization until end of treatment (up to approximately 2.5 years)

Duration of Response (DR)

DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date will be used. DR was calculated as [the date response ended (i.e. date of PD or death) - first CR or PR date + 1)]/30.4. DR would only be calculated for the subgroup of patients with an objective tumor response. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions.The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression. (NCT01740427)
Timeframe: From randomization until end of treatment (up to approximately 2.5 years)

Objective Response as Assessed by the Investigator

Objective Response (OR) defined as the overall complete response (CR) or partial response (PR) according to the RECIST v1.1. Objective Response Rate (ORR) is defined as proportion of patients with CR or PR relative to all randomized patients with measurable disease at baseline. Patients who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression. (NCT01740427)
Timeframe: From randomization until end of treatment (up to approximately 2.5 years)

Objective Response: Patients With Measurable Disease at Baseline as Assessed by the Investigator

The OR is defined as the overall CR or PR according to the RECIST v1.1. ORR is defined as proportion of patients with CR or PR relative to all randomized patients with measurable disease at baseline. Patients who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression. (NCT01740427)
Timeframe: From randomization until end of treatment (up to approximately 2.5 years)

Overall Survival (OS)

OS was defined as the time from date of randomization to date of death due to any cause. Participants without survival data beyond the date of their last follow-up were censored on the last date they were known to be alive. (NCT01740427)
Timeframe: From date of randomization until death due to any cause or censored, (assessed up to data cut-off date of 15-Nov-2021, approximately 8.7 years)

Progression-Free Survival (PFS) as Assessed by the Investigator.

PFS is defined as the time from the date of randomization to the date of the first documentation of objective tumor progression as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause in the absence of documented PD, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date - randomization date +1)/30.4. Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions, or the appearance of new lesions. (NCT01740427)
Timeframe: From randomization date to date of first documentation of progression OR death (up to approximately 2.5 years)

Corrected QT Interval (QTc) Time-matched Change From Baseline on Cycle 1 Day 14

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Time-matched change from baseline values were reported for QTc analysis population. (NCT01740427)
Timeframe: Time-matched triplicate ECGs were collected at 0 (predose), 2, 4, 6 and 8 hours on Day 0 and on Cycle1 Day14

Number of Participants With Laboratory Abnormalities by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade

Laboratory abnormalities included anemia, hemoglobin increased, neutrophils (absolute), platelets, white blood cells, alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia and hyponatremia. Laboratory abnormalities were graded by CTCAE version (v) 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life-threatening. Categories with at least 1 non-zero data values are reported. (NCT01740427)
Timeframe: From randomization up to 28 days after last dose of study drug (assessed up to data cut-off date of 15-Nov-2021, approximately 8.7 years)

Observed Plasma Trough Concentration (Ctrough) at Steady-State

Summary of Plasma Palbociclib Within-Patient Mean Steady-State Trough Concentrations. (NCT01740427)
Timeframe: 0 hour (predose) on Day 14 of cycles 1 and 2

Percentage of Participants With Corrected QT Interval (QTc)

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Percentage of participants with post-baseline maximum absolute values and maximum increase from baseline were summarized for the safety analysis population. (NCT01740427)
Timeframe: For safety monitoring triplicate ECGs were obtained at 0 hour (pre-dose) on Day 1 of Cycle 1, Day 14 of Cycles 1 and Cycle 2, then on Day 1 of Cycles 4, 7, and 10. ECGs beyond Cycle 10 were performed as clinically indicated

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)

An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization; resulted in persistent or significant disability or in congenital anomaly/birth defect. TEAE were events that occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Severity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening and Grade 5 = death related to AE. (NCT01740427)
Timeframe: From date of randomization up to 28 days after last dose of study drug, (assessed up to data cut-off date of 15-Nov-2021, approximately 8.7 years)

PFS by Tumor Tissue Biomarkers Status, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6)

"PFS by biomarker status by Investigator assessment. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.~Positive is defined as H-Score ≥1 and negative as H-Score <1. H-Score is calculated as the sum of the % of cells at each level of staining intensity (0, 1+, 2+, and 3+) multiplied by the staining intensity value: H-Score = (% at 0)*0 + (% at 1+)*1 + (% at 2+)*2 + (% at 3+)*3. H-Score values range from 0 to 300.~ER stands for estrogen receptor and Rb stands for retinoblastoma susceptibility gene product." (NCT01740427)
Timeframe: From randomization until end of treatment (up to approximately 24 Months)

Survival Probability at 1 Year, 2 Year and 3 Year

One, two or three-year survival probability was defined as the probability of survival 1 year, 2 or 3 years after the date of randomization. The survival probability was estimated using the Kaplan-Meier method and 2-sided 95% confidence interval (CI) was calculated using the product limit method. (NCT01740427)
Timeframe: 1, 2 and 3 years after randomization

Reviews

1 review available for letrozole and Neutropenia

Trials

10 trials available for letrozole and Neutropenia

Other Studies

4 other studies available for letrozole and Neutropenia