Anatomic Stage IV Breast Cancer AJCC v8, Estrogen Receptor Positive, HER2/Neu Negative, Metastatic Breast Carcinoma, Metastatic Malignant Neoplasm in the Bone, Progesterone Receptor Positive, Prognostic Stage IV Breast Cancer AJCC v8
Conditions
Brief summary
This phase II trial studies how well radiation therapy given with standard care palbociclib and hormone therapy work in treating patients with breast cancer that has spread from one part of the body to the bone. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Antihormone therapy, such as fulvestrant, letrozole, anastrozole, exemestane, or tamoxifen, may lessen the amount of estrogen made by the body. Giving radiation therapy, palbociclib, and hormone therapy may work better in treating breast cancer patients with bone metastasis.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the response rate three months post-conventionally fractionated radiotherapy, relative to baseline, for bone metastases in breast cancer patients receiving concurrent palbociclib and hormone therapy treatment. SECONDARY OBJECTIVES: I. To determine whether conventionally fractionated radiotherapy in combination with palbociclib and hormone therapy in breast cancer patients with bone metastases adversely increases the frequency and severity of palbociclib toxicities including grade 3 neutropenia. II. To determine whether radiotherapy in combination with palbociclib in breast cancer patients with bone metastases adversely increases the frequency and severity of radiotherapy toxicities including neurological and bone injury. III. To assess fatigue, quality of life, and depression before and after radiotherapy for bone metastases in metastatic breast cancer patients treated with palbociclib. IV. To determine progression free survival (PFS) and overall survival (OS) in breast cancer patients treated with palbociclib and concurrent radiotherapy to bone metastases. V. To evaluate the relationship between volume of irradiated bone and side effects of treatment, including leukopenia and neutropenia. TRANSLATIONAL RESEARCH OBJECTIVES: I. To collect, store, and analyze circulating tumor-derived deoxyribonucleic acid (ctDNA) in metastatic breast cancer patients treated with palbociclib and radiotherapy to bone metastases and to determine the relationship between ctDNA and responders versus non-responders, PFS, and OS. II. To collect, store, and analyze plasma for inflammatory cytokine measurements and determine their relationship with fatigue, depression, and quality of life before and after radiotherapy for bone metastases in metastatic breast cancer patients treated with palbociclib. III. To collect, store, and analyze ribonucleic acid (RNA) for gene expression to identify functional biology processes over-represented in genes differentially regulated among patients who develop toxicities versus those who do not and those who are responders versus those who are not and to identify transcriptional regulatory pathways driving observed differences in gene expression. OUTLINE: Patients undergo conventional radiation therapy over 5-10 days and receive palbociclib orally (PO) once daily (QD) on days 1-21. At the discretion of treating physician, patients also receive letrozole, anastrozole, exemestane, or tamoxifen PO QD on days 1-28, or fulvestrant intramuscularly (IM) on days 1 and 15 of cycles 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1 and 3 months.
Interventions
DRUGTamoxifen
Given PO
DRUGAnastrozole
Given PO
DRUGExemestane
Given PO
DRUGFulvestrant
Given IM
DRUGLetrozole
Given PO
DRUGPalbociclib
Given PO
RADIATIONRadiation Therapy
Undergo radiation therapy
Sponsors
Pfizer
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient Selection Guidelines: * Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up * Women of childbearing potential who are sexually active should be willing and able to use medically acceptable forms of contraception during protocol treatment Inclusion Criteria: * Pathologically confirmed metastatic breast cancer * Known estrogen, progesterone, and human epidermal growth factor receptor 2 (Her2) status of either primary tumor or metastasis * Metastatic estrogen receptor positive (ER+) or progesterone receptor positive (PR+), Her2/neu negative breast cancer patients with imaging confirming bone metastasis within 60 days of radiation simulation * Must be actively receiving palbociclib (125 or 100 mg PO daily for 3 weeks followed by a week off during 28-day cycles) plus one of the following hormone therapies for at least 28 days: * Fulvestrant (500 mg IM injection on days 1 and 15 cycle one and then on day one of each subsequent cycle (28 days) -or- * Letrozole (2.5 mg PO daily) -or- * Anastrozole (1 mg PO daily) -or- * Exemestane (25 mg PO daily) -or- * Tamoxifen (20 mg PO daily) * Patients must be willing and able to provide written informed consent/assent for the trial * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Karnofsky performance status (KPS) ≥ 60% within 60 days prior to registration * Must have bone disease that is either symptomatic (i.e. pain) or has a lytic or mixed lytic disease that can be assessed by computed tomography (CT), magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT within 60 days prior to radiotherapy on this study * One previous line of chemotherapy in advanced disease is allowed * Appropriate stage for study entry based on the following diagnostic workup: * History and physical examination within 60 days prior to registration * Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body PET/CT documenting metastatic disease prior to radiotherapy on this protocol or MRI documenting site of metastatic disease to be treated on protocol * Patient must be eligible for palliative radiotherapy (conventional radiation either 30 Gy in 10 fractions or 20 Gy in 5 fractions) for up to 4 separate anatomic regions containing bone metastases defined by 4 separate and not overlapping radiation plans * Absolute neutrophil count ≥ 1000/mcl (obtained within 14 days prior to registration on study) * Platelets ≥ 75,000 mm³ (obtained within 14 days prior to registration on study) * Hemoglobin ≥ 8.0 g/dl (obtained within 14 days prior to registration on study) (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0g/dl is acceptable) (obtained within 60 days prior to registration on study) * For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to radiation simulation * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry * Prior Treatment: * Patients may or may not have received radiotherapy or neoadjuvant or adjuvant chemotherapy in the treatment of their initial, non-metastatic breast cancer, but must be entered on study after their last dose of radiotherapy, last cycle of chemotherapy and biologic therapy (if applicable) and have sufficient resolution of side effects per physician assessment at time of radiotherapy * Patients must have not active wound healing issues from surgery and sufficient resolution of surgical side effects, per physician assessment, at time of radiotherapy * If patients have one line of chemotherapy for advanced disease, patients must be entered on study after their last dose of chemotherapy and have sufficient resolution of side effects per physician assessment at time of radiotherapy * Patients must have already initiated palbociclib (3 weeks on, 1 week off) and hormone therapy for at least 28 days prior to radiotherapy * During radiotherapy, no other investigation or commercial agents or therapy for cancer other than palbociclib, bisphosphonates, rank ligand inhibitors, and hormone therapy should be administered * Patients may have received bisphosphonates or rank ligand inhibitors prior to enrollment on study
Exclusion criteria
* Co-existing or prior invasive non-breast malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years * Previous radiation dose, date, fraction size, must be reported for prior invasive malignancy * Previous palliative radiation to the disease to be treated on protocol (including radiopharmaceuticals) * Patients prescribed stereotactic body radiation therapy (SBRT) for bone metastasis to be treated on this protocol will be excluded * Metastases to be treated on protocol located within 2 cm from a previously irradiated structure: * Spinal cord previously irradiated to \> 40 Gy (delivered in ≤ 3 Gy/fraction) * Brachial plexus previously irradiated to \> 50 Gy (delivered in ≤ 3 Gy/fraction) * Small intestine, large intestine, or stomach previously irradiated to \> 45 Gy (delivered in ≤ 3 Gy/fraction) * Brainstem previously irradiated to \> 50 Gy (delivered in ≤ 3 Gy/fraction) * Whole lung previously irradiated with prior V20 Gy \> 35% (delivered in ≤ 3 Gy/fraction) * Untreated brain metastases or unstable/progressive brain metastases (imaging of treated brain metastases must be performed within 28 days of registration for this protocol to confirm brain metastases stability) * Severe, active co-morbidity such as congestive heart failure (CHF) or unstable angina within last 6 months, transmural myocardial infarction within the last 6 months. Acute bacterial or fungal infection requiring intravenous (IV) antibiotics at time of registration, chronic obstructive pulmonary disease (COPD) or other respiratory illness requiring hospitalization at time of registration * Lactating females must cease expression of milk prior to registration * Temperature above 100.4° Fahrenheit * Human immunodeficiency virus (HIV) positive with cluster of differentiation 4 (CD4) count \< 200 cells/ microliter. HIV positive patients are eligible, provided they are receiving treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \> 200 cells/microliter within 28 days prior to registration. HIV testing is not required for eligibility for this protocol. This
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Up to 3 months post radiation | Response rate will be estimated as the number of responders divided by the number of patients evaluated for response. Among patients who present with pain, responders will be considered those patients who have a 2 point decrease in the Brief Pain Inventory (BPI), and among those who do not present with pain (radiotherapy due to risk of unstable fracture or cord compression), responders will be considered those without development of a pathologic fracture or neurologic compromise (cord compression) due to cancer on imaging. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | Up to 3 months post radiation | Adverse events, such as bone fracture following radiotherapy, any grade 3 toxicity (except neutropenia or leukopenia), grade 4 neutropenia, grade 4 leukopenia, grade 3 febrile neutropenia, or grade 3 brachial plexopathy or spinal cord injury, will be summarized descriptively. |
| Progression-free Survival (PFS) | Up to 44 months post radiation | PFS will be estimated using the Kaplan-Meier method. |
| Overall Survival (OS) | Up to 44 months post radiation | OS will be estimated using the Kaplan-Meier method. |
| Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation | Fatigue will be assessed before and after radiotherapy. The Multidimensional Fatigue Inventory (MFI) is a comprehensive self-report instrument designed to measure fatigue. It consists of 20 items rated on a 7-point scale and covers dimensions such as General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation, and Reduced Activity. Each question is score on a 1 to 5 scale, with 1 being 'yes, that is true' and 5 being 'No, that is not true'. The minimum score is 20 and the maximum score is100. The higher the score indicates fatigue. |
| Response Rate Incorporating BPI and Analgesic Measures According to International Bone Consensus Guideline Criteria | Up to 3 months post radiation | Response rate will be estimated as the number of responders divided by the number of patients evaluated for response. Among patients who present with pain, responders will be considered those patients who fulfill the International Bone Consensus response criteria using the BPI item rating maximum pain over the last 3 days at the index site and analgesic usage for the treated site within the last 24 hours prior to assessment. Among patients who do not present with pain (radiotherapy due to risk of unstable fracture or cord compression), responders will be considered those without development of a new pathologic fracture or worsening neurologic compromise (cord compression) due to cancer on imaging. |
| Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation | Quality of life will be assessed before and after radiotherapy. EORTC QLQ-BM22 measures four multi-item scales: painful sites, functional interference, painful characteristics, and psychosocial aspects Each item is scaled from 1 (not at all) to 4 (very much) and directly transformed into a 0-100 scale A higher score in symptom scales indicates greater distress. A higher score in functional scales indicates greater functional ability |
| Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation | Quality of life will be assessed before and after radiotherapy. The EORTC QLQ-C15-PAL measures seven scales: physical functioning, global health status, emotional functioning, fatigue, nausea/vomiting, appetite loss, and constipation For questions 1-14, each item is scaled from 1 (not at all) to 4 (very much) . For question 15 (global QoL), patients respond to a seven-point numerical scale from 1 (very poor overall) to 7 (excellent overall). The scale is scored from 0 to 100. A higher score in symptom scales indicates greater distress. A higher score in functional scales indicates greater functional ability. A higher score in global health status indicates a high quality of life. Each subscore is computed using the Addendum to the EORTC QLQ-C30 Scoring Manual: Scoring of the EORTC QLQ-C15-PAL. |
| Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation | Depression will be assessed before and after radiotherapy. The Hospital Anxiety and Depression Scale (HADS) is a 14-item tool used to screen for anxiety and depression, which commonly coexist. The HADS produces a subscale for anxiety (HADS-A) and a separate subscale for depression (HADS-D). The respondent rates each item on a 4-point scale ranging from 0 (absence) to 3 (extreme presence). The total score is out of 42, (21 per subscale) and the range is 0-42. Scores are derived by summing responses for each of the two subscales or for the scale as a whole. Higher scores indicate greater levels of anxiety or depression. The total HADS score may be regarded as a global measure of psychological distress. |
| Number of Participants With Adherence as Measured by Drug Diary | Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation | Adherence will be determined by number of days drug taken divided by number of days drug should have been taken over the time period of the study. |
| Quality of Life as Measured by Short Form Health Survey (SF-36) | Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation | Quality of life will be assessed before and after radiotherapy. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH) Each scale is the weighted sum of the questions in their section and are directly transformed into a 0-100 scale i.e., the minimum score is 0, maximum is 100 A higher score indicates less disability Total score on the SF-36 is the summation of all the eight scales |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation, Palbociclib, Hormone Therapy Patients undergo radiation therapy over 5-10 days and receive palbociclib PO QD on days 1-21. At the discretion of treating physician, patients also receive letrozole, anastrozole, exemestane, or tamoxifen PO QD on days 1-28, or fulvestrant IM on days 1 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Anastrozole: Given PO
Exemestane: Given PO
Fulvestrant: Given IM
Letrozole: Given PO
Palbociclib: Given PO
Radiation Therapy: Undergo radiation therapy
Tamoxifen: Given PO | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Radiation, Palbociclib, Hormone Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United States | 36 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 7 / 36 |
| other Total, other adverse events | 31 / 36 | 30 / 36 | 17 / 36 | 2 / 36 | 0 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
Response Rate
Response rate will be estimated as the number of responders divided by the number of patients evaluated for response. Among patients who present with pain, responders will be considered those patients who have a 2 point decrease in the Brief Pain Inventory (BPI), and among those who do not present with pain (radiotherapy due to risk of unstable fracture or cord compression), responders will be considered those without development of a pathologic fracture or neurologic compromise (cord compression) due to cancer on imaging.
Time frame: Up to 3 months post radiation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Response Rate | Responders | 29 Participants |
| Radiation, Palbociclib, Hormone Therapy | Response Rate | Non-responders | 6 Participants |
Secondary
Depression as Measured by Hospital Anxiety and Depression Scale (HADS)
Depression will be assessed before and after radiotherapy. The Hospital Anxiety and Depression Scale (HADS) is a 14-item tool used to screen for anxiety and depression, which commonly coexist. The HADS produces a subscale for anxiety (HADS-A) and a separate subscale for depression (HADS-D). The respondent rates each item on a 4-point scale ranging from 0 (absence) to 3 (extreme presence). The total score is out of 42, (21 per subscale) and the range is 0-42. Scores are derived by summing responses for each of the two subscales or for the scale as a whole. Higher scores indicate greater levels of anxiety or depression. The total HADS score may be regarded as a global measure of psychological distress.
Time frame: Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation
Population: Not all patients completed the measure at every timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Change (Last day of radiation - Pre-radiation) | -0.3 HADS score, both depression and anxiety | Standard Deviation 2 |
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Pre-radiation | 4.9 HADS score, both depression and anxiety | Standard Deviation 3.5 |
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Last day of radiation | 4.6 HADS score, both depression and anxiety | Standard Deviation 3.5 |
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | 1-month post radiation | 4.3 HADS score, both depression and anxiety | Standard Deviation 3.5 |
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | 3-month post radiation | 4.1 HADS score, both depression and anxiety | Standard Deviation 3.5 |
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Change (1-month post radiation - Pre-radiation) | -0.6 HADS score, both depression and anxiety | Standard Deviation 2.6 |
| Radiation, Palbociclib, Hormone Therapy | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Change (3-month post radiation - Pre-radiation) | -0.7 HADS score, both depression and anxiety | Standard Deviation 3.5 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Change (1-month post radiation - Pre-radiation) | -0.8 HADS score, both depression and anxiety | Standard Deviation 2.3 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | 3-month post radiation | 5.3 HADS score, both depression and anxiety | Standard Deviation 4 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Pre-radiation | 6.1 HADS score, both depression and anxiety | Standard Deviation 3.6 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Change (Last day of radiation - Pre-radiation) | -0.8 HADS score, both depression and anxiety | Standard Deviation 1.9 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Last day of radiation | 5.3 HADS score, both depression and anxiety | Standard Deviation 3.8 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | Change (3-month post radiation - Pre-radiation) | -0.8 HADS score, both depression and anxiety | Standard Deviation 3 |
| Treated, Pain Characteristics | Depression as Measured by Hospital Anxiety and Depression Scale (HADS) | 1-month post radiation | 5.2 HADS score, both depression and anxiety | Standard Deviation 3.6 |
Secondary
Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI)
Fatigue will be assessed before and after radiotherapy. The Multidimensional Fatigue Inventory (MFI) is a comprehensive self-report instrument designed to measure fatigue. It consists of 20 items rated on a 7-point scale and covers dimensions such as General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation, and Reduced Activity. Each question is score on a 1 to 5 scale, with 1 being 'yes, that is true' and 5 being 'No, that is not true'. The minimum score is 20 and the maximum score is100. The higher the score indicates fatigue.
Time frame: Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation
Population: Not all patients completed the measure at every timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | Pre-radiation | 55 Scores on a scale | Standard Deviation 16.4 |
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | Last Day of radiation | 53.6 Scores on a scale | Standard Deviation 13.8 |
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | 1-month post radiation | 54.0 Scores on a scale | Standard Deviation 16.6 |
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | 3-month post radiation | 52.3 Scores on a scale | Standard Deviation 15.9 |
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | Change (Last Day of Radiation - Pre-radiation) | 0.1 Scores on a scale | Standard Deviation 11.5 |
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | Change (1-month post radiation - Pre-radiation) | -0.4 Scores on a scale | Standard Deviation 15.2 |
| Radiation, Palbociclib, Hormone Therapy | Fatigue as Measured by The Multidimensional Fatigue Inventory (MFI) | Change (3-month post radiation - Pre-radiation) | -1.4 Scores on a scale | Standard Deviation 12.7 |
Secondary
Number of Participants With Adherence as Measured by Drug Diary
Adherence will be determined by number of days drug taken divided by number of days drug should have been taken over the time period of the study.
Time frame: Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation
Population: At each timepoint, there are a different number of patients analyzed due to missing data, patients that were lost to follow up or removed due to disease progression.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Number of Participants With Adherence as Measured by Drug Diary | Pre-radiation | 36 Participants |
| Radiation, Palbociclib, Hormone Therapy | Number of Participants With Adherence as Measured by Drug Diary | Last Day of radiation | 33 Participants |
| Radiation, Palbociclib, Hormone Therapy | Number of Participants With Adherence as Measured by Drug Diary | 1-month post radiation | 25 Participants |
| Radiation, Palbociclib, Hormone Therapy | Number of Participants With Adherence as Measured by Drug Diary | 3-month post radiation | 26 Participants |
| Treated, Pain Characteristics | Number of Participants With Adherence as Measured by Drug Diary | 3-month post radiation | 30 Participants |
| Treated, Pain Characteristics | Number of Participants With Adherence as Measured by Drug Diary | Pre-radiation | 36 Participants |
| Treated, Pain Characteristics | Number of Participants With Adherence as Measured by Drug Diary | 1-month post radiation | 29 Participants |
| Treated, Pain Characteristics | Number of Participants With Adherence as Measured by Drug Diary | Last Day of radiation | 35 Participants |
Secondary
Number of Participants With Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Adverse events, such as bone fracture following radiotherapy, any grade 3 toxicity (except neutropenia or leukopenia), grade 4 neutropenia, grade 4 leukopenia, grade 3 febrile neutropenia, or grade 3 brachial plexopathy or spinal cord injury, will be summarized descriptively.
Time frame: Up to 3 months post radiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Number of Participants With Adverse Events Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 31 Participants |
Secondary
Overall Survival (OS)
OS will be estimated using the Kaplan-Meier method.
Time frame: Up to 44 months post radiation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Overall Survival (OS) | 37.9 Months, estimated using the Kaplan-Meier |
Secondary
Progression-free Survival (PFS)
PFS will be estimated using the Kaplan-Meier method.
Time frame: Up to 44 months post radiation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Progression-free Survival (PFS) | 30.4 Months, estimated using the Kaplan-Meier |
Secondary
Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22)
Quality of life will be assessed before and after radiotherapy. EORTC QLQ-BM22 measures four multi-item scales: painful sites, functional interference, painful characteristics, and psychosocial aspects Each item is scaled from 1 (not at all) to 4 (very much) and directly transformed into a 0-100 scale A higher score in symptom scales indicates greater distress. A higher score in functional scales indicates greater functional ability
Time frame: Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation
Population: Not all patients completed the measure at every timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Pre-radiation | 28.0 EORT QLQ-BM22 score | Standard Deviation 21 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (1-month post radiation - Pre-radiation) | -9.4 EORT QLQ-BM22 score | Standard Deviation 15.7 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (Last Day of radiation - Pre-radiation) | -6.5 EORT QLQ-BM22 score | Standard Deviation 14.1 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Last Day of radiation | 21.5 EORT QLQ-BM22 score | Standard Deviation 20 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (3-month post radiation - Pre-radiation) | -10.7 EORT QLQ-BM22 score | Standard Deviation 15.8 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 1-month post radiation | 18.5 EORT QLQ-BM22 score | Standard Deviation 15.1 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 3-month post radiation | 17.7 EORT QLQ-BM22 score | Standard Deviation 14.4 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (1-month post radiation - Pre-radiation) | -9.0 EORT QLQ-BM22 score | Standard Deviation 25.9 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 3-month post radiation | 18.1 EORT QLQ-BM22 score | Standard Deviation 16.6 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 1-month post radiation | 22.2 EORT QLQ-BM22 score | Standard Deviation 24.6 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (Last Day of radiation - Pre-radiation) | -6.2 EORT QLQ-BM22 score | Standard Deviation 19.4 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (3-month post radiation - Pre-radiation) | -13.7 EORT QLQ-BM22 score | Standard Deviation 20 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Last Day of radiation | 25.0 EORT QLQ-BM22 score | Standard Deviation 23.7 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Pre-radiation | 31.2 EORT QLQ-BM22 score | Standard Deviation 26.5 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 3-month post radiation | 74.8 EORT QLQ-BM22 score | Standard Deviation 21 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Pre-radiation | 63.6 EORT QLQ-BM22 score | Standard Deviation 30.9 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Last Day of radiation | 73.4 EORT QLQ-BM22 score | Standard Deviation 25.8 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 1-month post radiation | 74.1 EORT QLQ-BM22 score | Standard Deviation 26.6 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (Last Day of radiation - Pre-radiation) | 9.8 EORT QLQ-BM22 score | Standard Deviation 18.7 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (1-month post radiation - Pre-radiation) | 10.5 EORT QLQ-BM22 score | Standard Deviation 29.8 |
| Treated, Functional Interference | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (3-month post radiation - Pre-radiation) | 11.9 EORT QLQ-BM22 score | Standard Deviation 23.1 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 1-month post radiation | 69.9 EORT QLQ-BM22 score | Standard Deviation 21.7 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (3-month post radiation - Pre-radiation) | 6.7 EORT QLQ-BM22 score | Standard Deviation 19 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (1-month post radiation - Pre-radiation) | 9.0 EORT QLQ-BM22 score | Standard Deviation 17.1 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Last Day of radiation | 68.4 EORT QLQ-BM22 score | Standard Deviation 19.8 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Pre-radiation | 61.0 EORT QLQ-BM22 score | Standard Deviation 20.9 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | Change (Last Day of radiation - Pre-radiation) | 7.4 EORT QLQ-BM22 score | Standard Deviation 18.7 |
| Treated, Psychological Aspects | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Metastases Module (EORTC QLQ-BM22) | 3-month post radiation | 68.1 EORT QLQ-BM22 score | Standard Deviation 23.3 |
Secondary
Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL)
Quality of life will be assessed before and after radiotherapy. The EORTC QLQ-C15-PAL measures seven scales: physical functioning, global health status, emotional functioning, fatigue, nausea/vomiting, appetite loss, and constipation For questions 1-14, each item is scaled from 1 (not at all) to 4 (very much) . For question 15 (global QoL), patients respond to a seven-point numerical scale from 1 (very poor overall) to 7 (excellent overall). The scale is scored from 0 to 100. A higher score in symptom scales indicates greater distress. A higher score in functional scales indicates greater functional ability. A higher score in global health status indicates a high quality of life. Each subscore is computed using the Addendum to the EORTC QLQ-C30 Scoring Manual: Scoring of the EORTC QLQ-C15-PAL.
Time frame: Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation
Population: Not all patients completed the measure at every timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | 1-month post radiation | 72.7 EORTC QLQ-C15-PAL score | Standard Deviation 20.4 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Change (Last Day of radiation - Pre-radiation) | -4.6 EORTC QLQ-C15-PAL score | Standard Deviation 21.3 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Last Day of radiation | 68.1 EORTC QLQ-C15-PAL score | Standard Deviation 20.5 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Change (1-month post radiation - Pre-radiation) | 0.0 EORTC QLQ-C15-PAL score | Standard Deviation 22.9 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | 3-month post radiation | 71.9 EORTC QLQ-C15-PAL score | Standard Deviation 20.5 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Change (3-month post radiation - Pre-radiation) | -0.5 EORTC QLQ-C15-PAL score | Standard Deviation 19.6 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Pre-radiation | 72.7 EORTC QLQ-C15-PAL score | Standard Deviation 19.6 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Change (3-month post radiation - Pre-radiation) | -13.8 EORTC QLQ-C15-PAL score | Standard Deviation 26 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Pre-radiation | 42.6 EORTC QLQ-C15-PAL score | Standard Deviation 28.9 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Last Day of radiation | 32.4 EORTC QLQ-C15-PAL score | Standard Deviation 28.4 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | 1-month post radiation | 28.7 EORTC QLQ-C15-PAL score | Standard Deviation 23.8 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | 3-month post radiation | 28.6 EORTC QLQ-C15-PAL score | Standard Deviation 23.8 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Change (Last Day of radiation - Pre-radiation) | -10.2 EORTC QLQ-C15-PAL score | Standard Deviation 25.3 |
| Treated, Pain Characteristics | Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care (EORTC QLQ-C15-PAL) | Change (1-month post radiation - Pre-radiation) | -13.9 EORTC QLQ-C15-PAL score | Standard Deviation 27.7 |
Secondary
Quality of Life as Measured by Short Form Health Survey (SF-36)
Quality of life will be assessed before and after radiotherapy. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH) Each scale is the weighted sum of the questions in their section and are directly transformed into a 0-100 scale i.e., the minimum score is 0, maximum is 100 A higher score indicates less disability Total score on the SF-36 is the summation of all the eight scales
Time frame: Pre-radiation on day 1, Last Day of radiation (5-10 days), 1 month post radiation, and 3 months post radiation, change last day of radiation, change 1 month post radiation, change 3 months post radiation
Population: Not all patients completed the measure at every timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | Pre-radiation | 41.8 Scores on a scale | Standard Deviation 8.8 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | Last Day of radiation | 42.0 Scores on a scale | Standard Deviation 8.2 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | 1-month post radiation | 44.0 Scores on a scale | Standard Deviation 8.1 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | 3-month post radiation | 44.0 Scores on a scale | Standard Deviation 8.2 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | Change (Last Day of radiation - Pre-radiation) | 0.2 Scores on a scale | Standard Deviation 4.7 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | Change (1-month post radiation - Pre-radiation) | 2.1 Scores on a scale | Standard Deviation 6.6 |
| Radiation, Palbociclib, Hormone Therapy | Quality of Life as Measured by Short Form Health Survey (SF-36) | Change (3-month post radiation - Pre-radiation) | 1.9 Scores on a scale | Standard Deviation 7.3 |
Secondary
Response Rate Incorporating BPI and Analgesic Measures According to International Bone Consensus Guideline Criteria
Response rate will be estimated as the number of responders divided by the number of patients evaluated for response. Among patients who present with pain, responders will be considered those patients who fulfill the International Bone Consensus response criteria using the BPI item rating maximum pain over the last 3 days at the index site and analgesic usage for the treated site within the last 24 hours prior to assessment. Among patients who do not present with pain (radiotherapy due to risk of unstable fracture or cord compression), responders will be considered those without development of a new pathologic fracture or worsening neurologic compromise (cord compression) due to cancer on imaging.
Time frame: Up to 3 months post radiation
Population: 27 participants were evaluable
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation, Palbociclib, Hormone Therapy | Response Rate Incorporating BPI and Analgesic Measures According to International Bone Consensus Guideline Criteria | Responders | 18 Participants |
| Radiation, Palbociclib, Hormone Therapy | Response Rate Incorporating BPI and Analgesic Measures According to International Bone Consensus Guideline Criteria | Non-responders | 2 Participants |
| Radiation, Palbociclib, Hormone Therapy | Response Rate Incorporating BPI and Analgesic Measures According to International Bone Consensus Guideline Criteria | Intermediate | 7 Participants |