UK Ibrance Patient Program (IPP) Study

Percentage of participants according to treatment lines during anytime between breast cancer (BC) diagnosis and index date were reported in this outcome measure. Treatment lines included: 1) 1st line where, palbociclib was prescribed as the first line treatment for MBC, 2) 1st line palbociclib added to letrozole where, palbociclib was prescribed as the first line treatment along with ongoing letrozole treatment which was prescribed more than 3 months prior to initiation of palbociclib, 3) 2nd line where palbociclib was prescribed as the second or later treatment line for MBC.

Time from letrozole was defined as duration from the start date of letrozole which was ongoing at the time of palbociclib treatment initiation up to the index date.

Number of participants with menopausal status as pre-menopausal, peri-menopausal, post-menopausal and not applicable (NA), during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Disease free interval was defined as the time from the date of last known neo-adjuvant hormone therapy to the date of MBC diagnosis.

Percentage of participants with de novo and recurrent metastatic disease, during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants with lymph nodes involvement during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. Data for this outcome measure is also presented by de novo status.

Number of lymph nodes involved during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. Data for this outcome measure is also presented by de novo status.

Number of participants with estrogen, progesterone and HER2 receptor status during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants who had rebiopsy during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants with tumor stages 0, 1, 2, 3 and 4, as per Tumor, Node, Metastasis (TNM) staging system, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. As per TNM staging system, tumor stage 0 indicates main tumor cannot be found; tumor stages 1, 2, 3 and 4 refers to the size and/or extent of the main tumor. The higher the number, the larger the tumor and/or the more it has spread into nearby tissues. Data for this outcome measure is also presented by de novo status.

Percentage of participants with nodal stages 0, 1, 2 and 3, as per TNM staging system, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. As per TNM staging system, nodal stage 0 indicates no cancer in regional lymph nodes; nodal stages 1= cancer has spread to 1 to 3 lymph nodes; nodal stage 2= cancer has spread to 4 to 9 lymph nodes, nodal stage 3= indicates the cancer has spread to 10 or more lymph nodes. Data for this outcome measure is also presented by de novo status.

Percentage of participants with metastasis stages 0 and 1, as per TNM staging system, during anytime between MBC disease diagnosis and index date were reported in this outcome measure. As per TNM staging system, metastasis stage 0 indicates cancer has not spread to other parts of the body; metastasis stage 1 indicates that the cancer has spread to distant parts of the body. Data for this outcome measure is also presented by de novo status.

Percentage of participants with tumor grades, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. Grades of disease was classified as grades 1, 2 and 3. As per TNM system, grade 1= well differentiated cells, low grade; grade 2= moderately differentiated cells, intermediate grade and grade 3= poorly differentiated cells, high grade.

Percentage of participants with Ki-67 protein proliferation index during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. The Ki-67 protein is a cellular marker for proliferation. Ki-67 is a protein in cells that increases as cells prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. More positive cells hasten in dividing and forming new cells. Proliferation index was measured by the percentage of cells staining for Ki-67.

The Ki-67 protein is a cellular marker for proliferation. Ki-67 is a protein in cells that increases as cells prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. More positive cells hasten in dividing and forming new cells. Proliferation index was measured by the percentage of cells staining for Ki-67.

ECOG PS measured quality of life of cancer participants on a 0 to 5 scale; 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity, ambulatory, able to carry out light/sedentary work; 2= ambulatory, capable of all self-care, unable to carry out any work activity, up >50 % of waking hours; 3= capable of only limited self-care, confined to bed/ chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. Higher scores indicated worsening of quality of life.

Percentage of participants with recurrence type during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants according to number of metastatic sites during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants according to location of metastases, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants with non-visceral location of metastases, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Number of participants according to metastatic sites with locoregional recurrence, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. Metastatic sites with locoregional recurrence included bone, breast, lung, pleural, regional lymph nodes and other sites.

Duration of BC disease was the time duration between date of BC disease diagnosis to palbociclib treatment initiation date.

Percentage of participants who received chemotherapy in adjuvant or neoadjuvant setting, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants who received chemotherapy in advanced, disease modifying or metastatic setting, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Number of lines of prior chemotherapy for metastatic disease during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants who received LHRH or chemotherapy, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants who received endocrine therapy in adjuvant or neoadjuvant setting, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Number of participants with types of endocrine therapy in adjuvant or neoadjuvant setting, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants who received endocrine therapy in advanced, disease modifying or metastatic setting, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants with type of endocrine therapy in advanced, disease modifying or metastatic setting, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Number of lines of prior endocrine therapy for metastatic disease during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Number of participants who received radiotherapy in advanced, disease modifying or metastatic setting, during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants who received concomitant medications, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure.

Number of participants with concomitant medications prescribed along with goserelin, during anytime between initial BC disease diagnosis and index date were reported in this outcome measure. Goserelin is the generic drug with a brand name Zoladex.

Number of participants according to number of prior treatments in metastatic setting, during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Number of participants according to number of prior chemotherapy and hormone therapy in metastatic setting, during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Number of participants according to number of prior chemotherapies in metastatic setting, during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Number of participants according to number of prior hormone therapies in metastatic setting, during anytime between MBC disease diagnosis and index date were reported in this outcome measure.

Percentage of participants with their starting dose of palbociclib were reported.

Percentage of participants who received endocrine therapy along with palbociclib were reported in this outcome measure. Endocrine therapy includes anastrozole, exemestane, fulvestrant and letrozole.

Percentage of participants with dose reductions and treatment discontinuation were reported in this outcome measure.

Number of participants with reasons for palbociclib discontinuation were reported in this outcome measure. Disease progression (PD) was defined as greater than or equal to (>=)20 percent (%) increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 millimeter (mm) or appearance of 1 or more new lesions. Adverse drug reactions (ADR) were defined as unintended, harmful events attributed to the use of drug. As per World Health Organisation (WHO) criteria for hematologic and nonhematologic toxicity grade 3 was defined as the severe/worst grade.

Percentage of participants with temporary discontinuation of palbociclib were reported in this outcome measure.

Percentage of participants according to time to dose reduction after palbociclib initiation in 1st line therapy were reported in this outcome measure.

Time to palbociclib discontinuation were observed in participants who permanently discontinued palbociclib and were reported in this outcome measure.

Number of participants according to lines of treatment after progression were reported in this outcome measure.

Doses of drugs prescribed for first 3 lines of treatment after progression were reported in this outcome measure.

Time duration of first 3 lines of treatment after progression up to lost to follow up or end of follow up period, whichever occurred first were reported in this outcome measure.

Number of 28-day cycles completed for palbociclib treatment were reported in this outcome measure.

Percentage of participants who received letrozole and fulvestrant along with palbociclib were reported in this outcome measure.

Progression free survival (PFS) was defined as the time from the index date to the date of first documented disease progression (PD) or death. PD was defined as >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm or appearance of 1 or more new lesions. Percentage of participants with progression free survival after index date were reported in this outcome measure.

Percentage of participants who were alive after palbociclib initiation were reported in this outcome measure.

CR was defined as disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures less than (<)10 mm; PR was defined as >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm or appearance of 1 or more new lesions.

SD was defined as neither shrinkage for CR or PR nor increase for PD taking as reference smallest sum of longest diameters since treatment start. Alive participants with no events were censored at date of last response assessment. CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10 mm; PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm or appearance of 1 or more new lesions.

PFS was defined as the time from the index date to the date of first documented PD or death. PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.

OS was defined as the time between the index date and the date of death from any cause. Participants who were still alive at the last date of data collection were censored.

Time to achieving BOR: time from index date until achievement of BOR: CR or PR, if CR was not achieved during follow-up. CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10 mm; PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm. Appearance of 1 or more new lesions; Alive participants with no events were censored at date of last response assessment.

Duration of follow-up period defined as the duration from index date until lost to follow up or end of follow up period, whichever occurred first, were reported in this outcome measure.

Percentage of participants with BR, PD and SD to palbociclib were reported in this outcome measure. BR was recorded for CR or PR. CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10 mm; PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm or appearance of 1 or more new lesions. SD: neither shrinkage for CR/PR nor increase for PD taking as reference smallest sum of longest diameters since treatment start. Alive participants with no events were censored at date of last response assessment.

Time to BR: time from index date until achievement of BR:CR or PR, if CR not achieved during follow-up. CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10 mm; PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm or appearance of 1 or more new lesions. Alive participants with no events were censored at date of last response assessment. Data is also presented by de novo status and relapse status.

Time to first response: time from index date until achievement of first response of CR or PR, if CR not achieved during follow-up. CR: disappearance of target, non-target lesions and normalization of tumor markers. Pathological lymph nodes had short axis measures <10 mm; PR: >=30% decrease in sum of measures (longest diameter for tumor lesions, short axis measure for nodes) of target lesions, taking reference baseline sum of diameters. Non-target lesions must be non-PD; PD: >=20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum must demonstrate absolute increase of at least 5 mm or appearance of 1 or more new lesions. Alive participants with no events were censored at date of last response assessment. Data is also presented by de novo status and relapse status.

Neutropenia is an abnormally low level of neutrophils with count <1500 neutrophils per microliter (mcL) in blood and was classified as per Common Toxicity Criteria (CTC) version 2.0 criteria: grade 1 (mild) with an absolute neutrophil count (ANC) of >=1500 to <2000 cells per mcL, grade 2 (moderate) with an ANC of >=1000 to <1500 cells per mcL, grade 3 (severe) with an ANC of >=500 to <1000 cells per mcL or grade 4 (severe) with an ANC lower than 500 cells per mcL. Percentage of participants with all grades, grade 3 and grade 4 were reported in this outcome measure. All grades category included grades 1 to grade 4.

Neutropenia is an abnormally low level of neutrophils with count <1500 neutrophils per mcL in blood and was classified as per CTC version 2.0 criteria: grade 1 (mild) with an ANC of >=1500 to <2000 cells per mcL, grade 2 (moderate) with an ANC of >=1000 to <1500 cells per mcL, grade 3 (severe) with an ANC of >=500 to <1000 cells per mcL or grade 4 (severe) with an ANC lower than 500 cells per mcL.

Neutropenia is an abnormally low level of neutrophils with count <1500 neutrophils per mcL in blood and was classified as per CTC version 2.0 criteria: grade 1 (mild) with an ANC of >=1500 to <2000 cells per mcL, grade 2 (moderate) with an ANC of >=1000 to <1500 cells per mcL, grade 3 (severe) with an ANC of >=500 to <1000 cells per mcL or grade 4 (severe) with an ANC lower than 500 cells per mcL.

Neutropenia is an abnormally low level of neutrophils with count <1500 neutrophils per mcL in blood and was classified as per CTC version 2.0 criteria: grade 1 (mild) with an ANC of >=1500 to <2000 cells per mcL, grade 2 (moderate) with an ANC of >=1000 to <1500 cells per mcL, grade 3 (severe) with an ANC of >=500 to <1000 cells per mcL or grade 4 (severe) with an ANC lower than 500 cells per mcL. Percentage of participants with grade 3 and 4 were reported in this outcome measure.

Febrile neutropenia (FN) was defined as an ANC of < 1.0 x 10^9 cells/L predicted to fall below 0.5 x 10^9 cells/L within 48 hours with fever or clinical signs of sepsis; fever and ANC were measured the same day or within ± 1 calendar day.

Percentage of participants with gastro-intestinal toxicities as diarrhea, nausea and vomiting after index date were reported in this outcome measure. As per CTC version 2.0 criteria, for diarrhea: grade 1 (mild)- less than 4 stools per day, grade 2 (moderate)- 4 to 6 stools per day, grade 3 (severe)- >=7 stools per day and grade 4 (life-threatening)- physiologic consequences requiring intensive care; Vomiting: grade 1 (mild)- 1 episode per day , grade 2 (moderate)- 2 to 5 episodes per day, grade 3 (severe)- >=6 episodes per day and grade 4 (life-threatening)- physiologic consequences requiring intensive care; Nausea: grade 1 (mild)- able to eat, grade 2 (moderate)- oral intake significantly reduced, grade 3 (severe)- no significant intake and requiring intravenous fluids.

Percentage of participants with at least one of the adverse events (neutropenia, diarrhea, nausea, and vomiting) after index date were reported in this outcome measure.

Absolute values for hematology parameter- hemoglobin, were reported in this outcome measure.

Absolute values for hematology parameters- white blood cell (WBC) counts, absolute neutrophil counts (ANC) and platelet counts (PLT), were reported in this outcome measure.

Absolute values for liver function parameters- Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP), were reported in this outcome measure.

Absolute values for liver function parameter- albumin, were reported in this outcome measure.

Absolute values for liver function parameter- bilirubin, were reported in this outcome measure.

Absolute values for bone profile parameters- calcium and phosphate were reported in this outcome measure.

Absolute values for clinical chemistry parameters- potassium, sodium and urea were reported in this outcome measure.

Absolute values for clinical chemistry parameter- creatinine, were reported in this outcome measure.

Percentage of participants with inpatient admissions and outpatient visits were reported in this outcome measure.

Duration of hospital stay was the time from the date of hospital entry to date of hospital discharge.

Percentage of participants who contacted CNS by phone calls and AOS either by phone calls or visits were reported in this outcome measure.