letrozole and Metastase

letrozole has been researched along with Metastase in 78 studies

Research

Studies (78)

Authors

Clinical Trials (21)

Trial Overview

Trial Outcomes

Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale

The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores

The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/ impairment Published weights are available that allow for the creation of a single summary score called the EQ-5D index, which basically ranges from 0 to 1 with low scores representing a higher level of dysfunction and 1 as perfect health. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Clinical Benefit Response (CBR)

CBR is defined as the overall complete response (CR), partial response (PR) , or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Clinical Benefit Response Rate (CBRR) is defined as the proportion of participants with CR, PR, or SD ≥24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received antitumor treatment other than the study medication prior to reaching a CR or PR, a best response of SD ≥24 weeks, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR and a best response of SD ≥24 weeks was counted as non-responders in the assessment of CBR. Per RECIST v1.1 for target lesions and assessed by MRI: CR, disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. (NCT01942135)
Timeframe: From randomization until end of treatment (assessed up to 12 months)

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 was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1)]/30.4. Kaplan-Meier estimate of median of the DR is provided below. No inferential statistical analysis were done for DR. The DR was only calculated for the participants with a CR or PR. (NCT01942135)
Timeframe: From randomization until end of treatment (assessed up to 12 months)

Objective Response (OR)

OR is defined as the overall complete response (CR) or partial response (PR) according to the RECIST version 1.1 Objective Response Rate (ORR) is defined as the proportion of participants with CR or PR relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions (longest for non-nodal and short axis for nodal target lesions); Overall Response (OR) = CR + PR. (NCT01942135)
Timeframe: From randomization until end of treatment (assessed up to 12 months)

Overall Survival (OS) - Number of Participants Who Died

OS is 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. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = [death date (censor date) - randomization date + 1]/30.4. No inferential statistical analysis were done because of the immaturity of the OS data. (NCT01942135)
Timeframe: From randomization until death (up to approximately 36 months)

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

PFS is 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 absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =[progression/death date(censor date) - randomization date + 1]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions. (NCT01942135)
Timeframe: From randomization date to date of first documentation of progression or death (assessed up to 12 months)

Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores

The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represent more severe symptoms. (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores

"The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant." (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores

The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning. (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores

"The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant." (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Ctrough for Fulvestrant

"Ctrough for Fulvestrant (if applicable). The method of dispersion applied here is percent coefficient of variation (%CV)." (NCT01942135)
Timeframe: Cycles 2/Day 1 and Cycle 3/Day 1

Ctrough for Goserelin

"Cmin for goserelin (if applicable). The method of dispersion applied here is percent coefficient of variation (%CV)." (NCT01942135)
Timeframe: Cycles 2/ Day 1 and Cycle 3/ Day 1

Observed Plasma Trough Concentration (Ctrough) for Palbociclib

"Ctrough for palbociclib (if applicable). The method of dispersion applied here is percent coefficient of variation (%CV)." (NCT01942135)
Timeframe: Cycle 1/Day 15 and Cycle 2/Day 15

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

An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. (NCT01942135)
Timeframe: From the signing of the informed consent until 28 days after the last dose of study medication up to 14 months

Survival Probabilities at Months 12, 24 and 36

One-, Two- or Three-year Survival Probability is defined as the probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate. Survival time was censored to last date the participant is known to be alive. (NCT01942135)
Timeframe: From randomization until death (assessed up to 36 months)

Time to Deterioration (TTD)

A time to event analysis was pre-specified for pain. An analysis of TTD in pain defined as time between baseline and first occurrence of increase of ≥10 points in pain. Deterioration will be defined increase in score of 10 points or greater from baseline. The Kaplan-Meier estimates of quartiles (time to deterioration) with 95% CI is mentioned below. (NCT01942135)
Timeframe: Baseline, Day 1 of Cycles 2 to 4, Day 1 of every alternate cycle after that until the end of treatment

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

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

Percentage of Participants Alive After 1 Year Post Palbociclib Treatment Initiation

Percentage of participants alive from date of initiation of palbociclib treatment through up to 2 or above progression-based lines of therapy were recorded and reported in this outcome measure. Percentage of participants who alive after 1 year post Palbociclib treatment initiation were based on the Kaplan-Meier estimate. (NCT03159195)
Timeframe: 1 Year (Month 12) post Palbociclib treatment initiation (data recorded during 4 years of retrospective observation period)

Percentage of Participants Alive After 2 Years Post Palbociclib Treatment Initiation

Percentage of participants alive from date of initiation of palbociclib treatment through up to 2 or above progression-based lines of therapy were recorded and reported in this outcome measure. Percentage of participants who alive after 2 years post Palbociclib treatment initiation were based on the Kaplan-Meier estimate. (NCT03159195)
Timeframe: 2 years (Month 24) post Palbociclib treatment initiation (data recorded during 4 years of retrospective observation period)

Percentage of Participants With Clinical Benefit Rate (CBR)

CBR was defined as the percentage of participants who achieved complete (where 'complete response' was recorded at any time on treatment) or partial response (where 'partial response' was recorded at any time on treatment), or stable disease at greater than equal to (>=) 24 weeks on palbociclib combination therapy. Stable disease was defined as no evidence of complete or partial response, and no progression on palbociclib therapy for 24 weeks or greater. Complete response - Complete resolution of all visible disease. Partial response - Partial reduction in size of visible disease in some or all areas without any areas of increase in visible disease. (NCT03159195)
Timeframe: From initiation of treatment up to disease progression (data recorded during 4 years of retrospective observation period)

Percentage of Participants With Objective Response Rate (ORR)

ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) on palbociclib combination therapy according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression due to any cause. Complete response: complete resolution of all visible disease. Partial response: partial reduction in size of visible disease in some or all areas without any areas of increase in visible disease. (NCT03159195)
Timeframe: From initiation of treatment up to disease progression (data recorded during 4 years of retrospective observation period)

Percentage of Participants With Progression Free Survival (PFS) at Month 12

PFS was defined as the time from palbociclib combination treatment initiation until 1) clinician documented disease progression (PD) while on palbociclib, 2) death, 3) start of a new therapy line after final palbociclib dose, if the reason for discontinuation of palbociclib was disease progression, or 4) last available follow-up, whichever occurred first. Participants who did not experience a progression event (items 1, 2 and 3) were censored at date of last available follow-up. PFS (in months) was calculated as (first event date - palbociclib initiation date + 1)/30.4. Progressive disease - An increase in visible disease and/or presence of any new lesions; included cases where the clinician indicated progressive disease. Percentage of participants with PFS events at 12 months based on the Kaplan-Meier estimate were reported. (NCT03159195)
Timeframe: Day 1 of palbociclib combination treatment up to Month 12 (data recorded during 4 years of retrospective observation period)

Percentage of Participants With Progression Free Survival at Month 24

PFS was defined as the time from palbociclib combination treatment initiation until 1) clinician documented disease progression (PD) while on palbociclib, 2) death, 3) start of a new therapy line after final palbociclib dose, if the reason for discontinuation of palbociclib was disease progression, or 4) last available follow-up, whichever occurred first. Participants who did not experience a progression event (items 1, 2 and 3) were censored at date of last available follow-up. PFS (in months) was calculated as (first event date - palbociclib initiation date + 1)/30.4. Progressive disease - An increase in visible disease and/or presence of any new lesions; included cases where the clinician indicated progressive disease. Percentage of participants with PFS events at 24 months based on the Kaplan-Meier estimate were reported. (NCT03159195)
Timeframe: Day 1 of palbociclib combination treatment up to Month 24 (data recorded during 4 years of retrospective observation period)

Percentage of Participants With Best Overall Response

Best overall response was defined as the percentage of participants who achieved complete (where 'complete response' was recorded at any time on treatment), partial response (where 'partial response' was recorded at any time on treatment) and stable disease at greater than equal to (>=) 24 weeks on palbociclib combination therapy. Stable disease was defined as no evidence of complete or partial response, and no progression on palbociclib therapy for 24 weeks or greater. (NCT03159195)
Timeframe: From initiation of treatment up to disease progression (data recorded during 4 years of retrospective observation period)

Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator

CB is defined as the percentage of participants with evidence of confirmed CR, PR, or stable disease (SD) for at least 6 months. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the baseline measurement. (NCT00073528)
Timeframe: Up to 46 months

Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator

CB is defined as the percentage of participants with evidence of confirmed CR, PR, or stable disease (SD) for at least 6 months. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the baseline measurement. (NCT00073528)
Timeframe: Up to 46 months

Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator

Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD) until the first documented sign of disease progression or death due to any cause. The assessments of CR or PR required confirmation using bone scans. (NCT00073528)
Timeframe: Up to 46 months

Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator

Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD) until the first documented sign of disease progression or death due to any cause. The assessments of CR or PR required confirmation using bone scans. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With Evidence of Brain Metastases From the ITT Population

The confirmation criteria for the evidence of brain metastases was the incidence of lesions occurring within any part of the central nervous system (CNS) as evidenced by radiological scans. Metastases are defined as the spread of cancer from one part of the body to another. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population

The confirmation criteria for the evidence of brain metastases was the incidence of lesions occurring within any part of the central nervous system (CNS) as evidenced by radiological scans. Metastases are defined as the spread of cancer from one part of the body to another. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator

PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions. (NCT00073528)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months

Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced or Metastatic Breast Cancer as Assessed by the Investigator

PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. The date of documented PD is defined as the date of radiological PD as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0), PD is defined as a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions. (NCT00073528)
Timeframe: From the date of randomization until the date of the first documented progression or date of death from any cause, whichever came first, assessed for up to 46 months

Overall Survival in the HER2-Positive Population

Overall survival was defined as the time from randomization until death due to any cause. (NCT00073528)
Timeframe: From date of randomization until date of death due to any cause, assessed up to 46 months

Overall Survival in the ITT Population

Overall survival was defined as the time from randomization until death due to any cause. (NCT00073528)
Timeframe: From date of randomization until date of death due to any cause, assessed up to 46 months

Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator

OR is defined as the percentage of participants achieving either a confirmed complete response (CR) or partial response (PR). Response was assessed via Response Evaluation criteria in Solid Tumors (RECIST). The percentage of participants with response was calculated by using the formula: 100 * (number of participants with CR + number of participants with PR)/total number of participants. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. (NCT00073528)
Timeframe: Up to 46 months

Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator

OR is defined as the percentage of participants achieving either a confirmed complete response (CR) or partial response (PR). Response was assessed via Response Evaluation criteria in Solid Tumors (RECIST). The percentage of participants with response was calculated by using the formula: 100 * (number of participants with CR + number of participants with PR)/total number of participants. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. (NCT00073528)
Timeframe: Up to 46 months

PFS in Participants in the ITT Population as Assessed by the Investigator

PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions. (NCT00073528)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months

Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator

PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions. (NCT00073528)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months

Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator

TTP is defined as the interval between the date of randomization and the earliest date of disease progression or death due to breast cancer. Disease progression was based on the assessments by the Investigator. (NCT00073528)
Timeframe: Up to 46 months

Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive

Time to seroconversion was defined as the time from the date of randomization until the first instance of serum HER2 (>15 ng/mL) on two consecutive occasions. (NCT00073528)
Timeframe: Up to 46 months

TTP for Participants From the ITT Population as Assessed by the Investigator

TTP is defined as the interval between the date of randomization and the earliest date of disease progression or death due to breast cancer. Disease progression was based on the assessments by the Investigator. (NCT00073528)
Timeframe: Up to 46 months

Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data

Quality of Life (QOL) was assessed using the FACT-B questionnaire, which is a 37-item (27 general and 10 breast cancer-specific questions) self-reporting instrument consisting of 5 dimensions: physical-, social/family-, emotional-, functional-well being, and a breast cancer subscale. Higher scores on the FACT-B scales indicate a higher QOL; each ranging from 0 (not at all) to 4 (very much). The score is transformed for FACT-B and results in a total score ranging from 0 to 144. The FACT-B is designed to measure multidimensional QOL in participants with breast cancer. (NCT00073528)
Timeframe: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit

Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data

FACT-G is a subscale of the FACT-B QOL questionnaire and consists of 27 questions grouped into 4 domains that measure a participant's physical, functional, social and family, and emotional well-being. FACT-G is assessed on a five-point Likert-type scale, with scores ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). The total score is calculated as the sum of the item scores on the subscale; the total ranges from 0 to 108, with higher score indicating a better quality of life. (NCT00073528)
Timeframe: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit

Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data

The TOI score is the sum of the physical well-being, functional well-being, and breast cancer unweighted subscale scores. The total TOI score ranges from 0 to 92, with higher scores representing a better quality of life. (NCT00073528)
Timeframe: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit

All Collected Deaths

"On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 663.9 weeks (treatment duration ranged from 0.1 to 659.9 weeks).~Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 14 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored." (NCT00073528)
Timeframe: up to 663 weeks (on-treatment), up to approximately 14 years (study duration)

Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive

Participants who had a HER2-negative tumor status based on baseline tissue with baseline serum HER2 ECD values =<15 ng/mL but later had at least two consecutive serum HER2 ECD values >15 ng/mL experienced seroconversion. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores

A minimally important difference (MID) is the smallest difference in a score for a measure of QOL that corresponds to a difference in function or clinical course. Responders are defined as participants with an MID => 8 for the FACT-B score, and an MID =>6 for the FACT-G and TOI scores. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits

Quality of Life (QOL) was assessed using the FACT-B questionnaire, which was a 37-item (27 general and 10 breast cancer-specific questions) self-reporting instrument consisting of 5 dimensions: physical-, social/family-, emotional-, functional-well being, and a breast cancer subscale. Higher scores on the FACT-B scales (each ranging from 0 [not at all] to 4 [very much]) indicate a higher QOL. The score is transformed for FACT-B and results in a total score ranging from 0 to 144. Complete: completing at least 1 question from FACT-B. (NCT00073528)
Timeframe: Day 1 (baseline) visit; Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192 visits; conclusion/withdrawal visit

Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status

Clinical benefit: participants with CR, PR, or SD for =>6-month period. FISH testing measures the amount of the HER2 gene in each cell. This gene is responsible for the overproduction of the HER2 protein. FISH-positive: excessive amounts of the gene are present; FISH-negative: normal levels of the gene are present. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity

IHC is a commonly used test to assess the amount of the HER2 receptor protein on the surface of the cancer cells. The IHC test results in a score of 0 to 3+, which indicates the amount of HER2 receptor protein on the cells in a sample of breast cancer tissue. Tissue scores of 0 to 1+ indicate HER2 negativity; scores of 2+ and 3+ indicate HER2 positivity. Clinical benefit is defined as participants with CR, PR, or SD for =>6-month period. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator

Participants were stratified based on site of disease at screening (SDS) (soft tissue or visceral or bone-only disease) and prior adjuvant endocrine therapy (PAET) (discontinuation interval [DI] =>6 months or DI <6 months). OR is defined as the number of participants achieving either a confirmed CR or PR. Response was assessed via RECIST. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. DI is defined as the time period from stopping the PEAT to the randomization date. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator

Participants were stratified based on site of disease at screening (SDS) (soft tissue or visceral or bone-only disease) and prior adjuvant endocrine therapy (PAET) (discontinuation interval [DI] =>6 months or DI <6 months). OR is defined as the number of participants achieving either a confirmed CR or PR. Response was assessed via RECIST. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. DI is defined as the time period from stopping the PEAT and the randomization date. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With Response in Participants With Baseline Serum HER2 Extracellular Domain (ECD) Baseline Values Greater Than 15 Nanograms Per Milliliter (ng/mL) and 15 ng/mL or Lower

The HER2 ECD is a glycoprotein that can be shed from the cell surface into the blood of normal individuals and can be elevated in different pathologic conditions. The serum HER2 ECD level generally reflects the tissue HER2 status. The HER2 ECD is quantified in serum with an enzyme-linked immunosorbent assay (ELISA). Non-Evaluable (NE): any participant who could not be classified as CR, PR, SD, or PD. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator.

CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum LD since the baseline measurement. The best overall response is defined as the best response recorded from the start of treatment until disease progression/recurrence. PD: presence of target lesions, non-target lesions, and/or new lesions. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator.

CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum LD since the baseline measurement. The best overall response is defined as the best response recorded from the start of treatment until disease progression/recurrence. PD: presence of target lesions, non-target lesions, and/or new lesions. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline

EGFR is a cell surface receptor tyrosine kinase expressed in certain types of tumors. Depending upon the staining intensity, EGFR was graded as follows: 0=absence of membrane staining above background in all tumor cells; EGFR-positive=staining is defined as any IHC staining of tumor cell membranes above background level, whether it is complete or incomplete circumferential staining (1+, 2+, 3+). (NCT00073528)
Timeframe: Baseline

Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator

Time to response is defined as the time from randomization until the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sume of the LD of target lesions, taking as reference the baseline sum LD) (whichever status was recorded first). The assessments of CR or PR required confirmation using bone scans. (NCT00073528)
Timeframe: Up to 46 months

Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator

Time to response is defined as the time from randomization until the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sume of the LD of target lesions, taking as reference the baseline sum LD) (whichever status was recorded first). The assessments of CR or PR required confirmation using bone scans. (NCT00073528)
Timeframe: Up to 46 months

Anti-tumor Effect in Terms of Pathologic CR (pCR) Rate to Neoadjuvant Chemotherapy (Cohort B)

The primary aim is to assess the anti-tumor effect in terms of pathologic CR rates of neo-adjuvant chemotherapy in patients with T2-T4c, any N, M0 breast cancer (by clinical staging) who are endocrine therapy resistant (that is, their Ki-67 level is >10 after 2-4 week of neo-adjuvant endocrine therapy alone). The pCR rate (percentage) for neo-adjuvant chemotherapy is defined as 100 times the number of eligible patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary or sentinel lymph nodes divided by the total number of eligible patients who received neo-adjuvant chemotherapy. (NCT00265759)
Timeframe: Up to 18 weeks

Clinical Response (Complete or Partial Response) Rate (Cohort A)

The clinical response rate (percentage) of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose disease meets the WHO criteria for complete or partial response prior to surgery divided by the total number of eligible patients randomized to that treatment. For each treatment arm, a 95% binomial confidence interval will be constructed for the true clinical response rate. Complete Response (CR): The disappearance of all known disease based on a comparison between the measurements at baseline and the Week 16 visit. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) based on a comparison between the measurements at baseline and the Week 16 visit. In addition there can be no appearance of new lesions or progression of any lesion. (NCT00265759)
Timeframe: Up to 18 weeks

Rate of Improved Surgical Outcome for Patients Considered Marginal for Breast Conservation Surgery Prior to Therapy (Cohort A)

The rate (percentage) of improved surgical outcome for patients considered marginal for breast conservation surgery prior to therapy for Cohort A is reported below for each treatment arm. Breast conservation surgery (not mastectomy) as the most extensive surgery performed for a patient is considered an improvement in surgical outcome. (NCT00265759)
Timeframe: At time of surgery up to 18 weeks

Rate of Improved Surgical Outcome for Patients Designated as Candidates for Mastectomy Prior to Therapy (Cohort A)

Rate (percentage) of Improved surgical outcome for patients designated as candidates for mastectomy prior to therapy (Cohort A). Breast conservation surgery (not mastectomy) as the most extensive surgery performed for a patient is considered an improvement in surgical outcome. (NCT00265759)
Timeframe: At time of surgery up to 18 weeks

Rate of Lymph Node Involvement (LNI) (Cohort A)

For those patients who undergo a sentinel lymph node dissection or an axillary lymph node dissection (at least 6 nodes examined with Hematoxylin & Eosin Staining), the LNI rate (percentage) is defined as 100 times the proportion of eligible patients randomized to that treatment with at least one positive node. For each neo-adjuvant endocrine treatment, a 95% binomial confidence interval will be constructed for its true LNI rate. (NCT00265759)
Timeframe: At time of surgery up to 18 weeks

The Pathologic Complete Response (pCR) Rate (Cohort A)

The pathologic complete response is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes. The pathologic complete response rate (percentage) of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose surgical specimen is such that there is no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes divided by the total number of eligible patients randomized to that treatment. For each neo-adjuvant endocrine treatment pair, a 95% binomial confidence interval will be constructed for the true difference in the pCR between these 2 treatments. (NCT00265759)
Timeframe: At time of surgery up to 18 weeks

Toxicity (Cohort A)

Incidence of the most common grade 3+ toxicities reported to be probably, possibly, or definitely related to treatment as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (Cohort A) At each treatment evaluation, the type, severity, and attribution of each adverse event reported will be assessed using the NCI-CTCAE definitions. For each treatment, the percentage of patients who developed a severe (grade 3+) toxicity considered possibly, probably or definitively related to treatment will be determined. (NCT00265759)
Timeframe: Up to 30 days after drug therapy

Reviews

25 reviews available for letrozole and Metastase

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18 trials available for letrozole and Metastase

Other Studies

35 other studies available for letrozole and Metastase