Early Breast Cancer
Conditions
Brief summary
This is a randomized, multicenter, open-label, two-arm, Phase II study to evaluate the efficacy, safety, and pharmacokinetics of giredestrant versus anastrozole (in the window-of-opportunity phase) and giredestrant plus palbociclib compared with anastrozole plus palbociclib (in the neoadjuvant phase) in postmenopausal women with untreated, estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, early breast cancer. The study consists of a screening period of up to 28 days, a window-of-opportunity phase for 14 days, followed by a neoadjuvant treatment phase for 16 weeks (four 28-day cycles), surgery, and an end of study visit (28 days after the final dose of study treatment).
Interventions
DRUGGiredestrant
During the window-of-opportunity phase (first 2 weeks) giredestrant will be taken orally once per day (QD) as a single agent. During the neoadjuvant treatment phase, giredestrant will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib.
DRUGAnastrozole
During the window-of-opportunity phase (first 2 weeks), anastrozole 1 mg will be taken orally QD as a single agent. During the neoadjuvant treatment phase, anastrozole 1 mg will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib.
DRUGPalbociclib
During the neoadjuvant treatment phase, palbociclib 125 mg will be taken orally QD on Days 1-21 of a 28-day cycle for a total of 4 cycles.
PROCEDURESurgery
Surgery must be performed within a maximum of 14 days after the final cycle in the neoadjuvant treatment phase and ideally should occur as soon as possible after the last dose of study treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women age ≥18 years * Histologically confirmed operable or inoperable invasive breast carcinoma * Candidate for neoadjuvant treatment and considered appropriate for endocrine therapy * Willingness to undergo breast surgery after neoadjuvant treatment and to provide three mandatory tumor samples * Documented estrogen receptor (ER)-positive tumor in accordance to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al.2020), assessed locally and defined as ≥1% of tumor cells stained positive on the basis of the most recent tumor biopsy * Documented progesterone receptor status (positive or negative) as per local assessment * Documented human epidermal growth factor receptor-2 (HER2)-negative tumor in accordance to 2018 ASCO/CAP guidelines (Wolff et al. 2018), assessed locally on the most recent tumor biopsy * Ki67 score ≥5% analyzed centrally or locally * Eastern Cooperative Oncology Group Performance Status 0-1 * Adequate organ function
Exclusion criteria
* Stage IV (metastatic) breast cancer * Inflammatory breast cancer (cT4d) * Bilateral invasive breast cancer * History of invasive breast cancer, ductal carcinoma in situ or lobular carcinoma in situ and other malignancy within 5 years prior to screening * Previous systemic or local treatment for the primary breast cancer currently under investigation * History of any prior treatment with aromatase inhibitors (AIs), tamoxifen, selective estrogen receptor down regulator, or cyclin-dependent kinase 4 and 6 inhibitors * Major surgery within 4 weeks prior to randomization * Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study * History of allergy to anastrozole, or palbociclib or any of its excipients * Known issues with swallowing oral medication * History of documented hemorrhagic diathesis, coagulopathy, or thromboembolism * Active cardiac disease or history of cardiac dysfunction * Current treatment with medications that are well known to prolong the QT interval * Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery including gastric resection * Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives prior to randomization * Known HIV infection * Serious infection requiring oral or IV antibiotics, or other clinically significant infection within 14 days prior to screening * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Percent Change in Ki67 Scores From Baseline to Week 2 | Baseline, Week 2 | Ki67 is a proliferation biomarker with prognostic value in ER-positive breast cancer. Ki67 scores were centrally assessed with immunohistochemistry and defined as a percentage of positively stained tumor cell nuclei among the total number of tumor cells assessed, with a potential range of 0-100%. A score of 0% indicates no tumor cell nuclei with Ki67 staining and a score of 100% indicates all tumor cell nuclei are positively stained with Ki67. The relative percentage change was calculated using Ki67 scores at Baseline and Week 2. Relative Percent Change was defined as Week 2 Ki67 percentage score/Baseline Ki67 percentage score\*100. A smaller value of relative percentage change indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Cell Cycle Arrest (CCCA) Rate at Week 2 | Week 2 | CCCA was defined as the percentage of participants with centrally assessed Ki67 scores ≤2.7%. The CCCA rate at Week 2 was summarized. |
| Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | From baseline up to 28 days after the last dose (up to approximately 24 weeks) | AE is any untoward medical occurrence in clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign, symptom/disease temporally associated with use of a medicinal product, whether or not related to medicinal product. Preexisting conditions which worsen during a study also considered as AEs. Severity of AEs was determined per NCI CTCAE v5.0. Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care activities of daily living; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE. |
| Change From Baseline in Respiratory Rate Over Time | Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks) | Respiratory rate was measured while the participant was in a seated position. |
| Change From Baseline in Pulse Rate Over Time | Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks) | Pulse rate was measured while the participant was in a seated position. |
| Change From Baseline in Systolic Blood Pressure Over Time | Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks) | Systolic blood pressure was measured while the participant was in a seated position. |
| Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator | Baseline up to Cycle 4 Day 1 (each cycle is 28 days) | ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR), as determined by the investigator according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Ultrasound and clinical exam were used to assess response. CR per mRECIST was defined as the disappearance of all target lesions. PR per mRECIST was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. An estimate of ORR and its 95% confidence interval (CI) was calculated using the Clopper-Pearson method. |
| Change From Baseline in Body Temperature Over Time | Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks) | — |
| Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | From baseline up to 28 days after the last dose (up to approximately 24 weeks) | Hematology test parameters were measured per NCI CTCAE v5.0. Grade 0 is normal, and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Number of participants with shift in the hematology values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. A marked reference range for hemoglobin 12.3-15.3 grams per deciliter (g/dL), lymphocytes absolute (Abs) 1.0-4.8 10\^3/microliters (uL), neutrophils total, Abs, 1.8-8.5 10\^3/uL, platelet 100-450 10\^9/liter (L), total leukocyte 4.4-11 10\^9/L. |
| Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | From baseline up to 28 days after the last dose (up to approximately 24 weeks) | Blood chemistry parameters were measured per NCI CTCAE v5.0. Grade 0=normal, and Grades 1 to 4 represent worsening levels of parameter outside of normal range in the specified direction of abnormality (high & low are above & below the range, respectively). Number of participants with shift in blood chemistry values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. Marked reference range for albumin 32-45 grams per liter (g/L), alkaline phosphatase 20-130 units per liter (U/L), serum glutamic pyruvic transaminase (SGPT)/ alanine transaminase (ALT) 4-36 U/L, serum glutamic oxaloacetic transaminase (SGOT)/ aspartate transaminase (AST) 8-33 U/L, calcium 2.3-2.74 millimoles per liter (mmol/L), cholesterol 3.88-6.47mmol/L, creatinine 6-12 milligrams per liter (mg/L), glucose 3.9-6.1 mmol/L, potassium 3.5-5.0 mmol/L, sodium 135-147 mmol/L, bilirubin 2-21 micromoles per liter (μmol/L), triglycerides 0.11-2.15 mmol/L, & uric acid 2.7-7.3 milligrams per deciliter (mg/dL). |
| Plasma Concentration of Giredestrant at Specified Timepoints | Window of Opportunity Phase: Day 1 (3 hours Postdose) and Day 15 (Predose) during Cycle 0 (the 15-day period in Window of Opportunity Phase is called Cycle 0 for PK analysis); Neoadjuvant Phase: Cycle 2 Day 1, Predose | — |
| Change From Baseline in Diastolic Blood Pressure Over Time | Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks) | Diastolic blood pressure was measured while the participant was in a seated position. |
Countries
Australia, Brazil, Germany, Hungary, Poland, Russia, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Recruitment details
Participants took part in this study at 64 investigative sites in Australia, Brazil, Germany, Hungary, Korea, Poland, Russia, Spain, Taiwan, the United States, and Ukraine, from 4 September 2020 to 24 November 2021.
Pre-assignment details
A total of 264 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Giredestrant + Palbociclib Participants received giredestrant, 30 mg, orally, QD, during the window-of-opportunity phase of two weeks. During the neoadjuvant treatment phase, participants received giredestrant, 30 mg, orally, QD on Days 1-28 of each 28-day cycle for a total of 4 cycles in combination with palbociclib, 125 mg, administered orally, QD on Days 1-21 of each 28-day cycle for a total of 4 cycles. | 112 |
| Anastrozole + Palbociclib Participants received anastrozole, 1 mg, orally, QD, during the window-of-opportunity phase of two weeks. During the neoadjuvant treatment phase, participants received anastrozole, 1 mg, orally, QD on Days 1-28 of each 28-day cycle for a total of 4 cycles in combination with palbociclib, 125 mg, administered orally, QD on Days 1-21 of each 28-day cycle for a total of 4 cycles. | 109 |
| Total | 221 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Progressive Disease | 0 | 4 |
| Overall Study | Protocol Deviation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Giredestrant + Palbociclib | Anastrozole + Palbociclib | Total |
|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 7.9 | 62.4 years STANDARD_DEVIATION 9.3 | 62.8 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 11 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 98 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Ki67 Scores | 37.92 percent Ki67 score | 41.66 percent Ki67 score | 39.76 percent Ki67 score |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 9 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) White | 100 Participants | 94 Participants | 194 Participants |
| Sex: Female, Male Female | 112 Participants | 109 Participants | 221 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 112 | 0 / 109 |
| other Total, other adverse events | 99 / 112 | 93 / 109 |
| serious Total, serious adverse events | 5 / 112 | 2 / 109 |
Outcome results
Primary
Relative Percent Change in Ki67 Scores From Baseline to Week 2
Ki67 is a proliferation biomarker with prognostic value in ER-positive breast cancer. Ki67 scores were centrally assessed with immunohistochemistry and defined as a percentage of positively stained tumor cell nuclei among the total number of tumor cells assessed, with a potential range of 0-100%. A score of 0% indicates no tumor cell nuclei with Ki67 staining and a score of 100% indicates all tumor cell nuclei are positively stained with Ki67. The relative percentage change was calculated using Ki67 scores at Baseline and Week 2. Relative Percent Change was defined as Week 2 Ki67 percentage score/Baseline Ki67 percentage score\*100. A smaller value of relative percentage change indicates improvement.
Time frame: Baseline, Week 2
Population: Efficacy-evaluable population included participants with Ki67-evaluable tumor specimens at baseline and Week 2. Participants with missing central Ki67 scores at baseline and/or Week 2 were excluded from the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Giredestrant + Palbociclib | Relative Percent Change in Ki67 Scores From Baseline to Week 2 | 25 percent change |
| Anastrozole + Palbociclib | Relative Percent Change in Ki67 Scores From Baseline to Week 2 | 33 percent change |
p-value: 0.0433t-test, 2 sided
Secondary
Change From Baseline in Body Temperature Over Time
Time frame: Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 1 Day 1 | 0.07 Celsius (C) | Standard Deviation 0.39 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 2 Day 15 | -0.03 Celsius (C) | Standard Deviation 0.37 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Baseline | 36.35 Celsius (C) | Standard Deviation 0.41 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 3 Day 1 | -0.04 Celsius (C) | Standard Deviation 0.42 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 1 Day 15 | 0.01 Celsius (C) | Standard Deviation 0.41 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Day of Surgery | 0.06 Celsius (C) | Standard Deviation 0.39 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 4 Day 1 | -0.03 Celsius (C) | Standard Deviation 0.37 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at End of Study | 0.05 Celsius (C) | Standard Deviation 0.39 |
| Giredestrant + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 2 Day 1 | 0.03 Celsius (C) | Standard Deviation 0.4 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at End of Study | -0.04 Celsius (C) | Standard Deviation 0.48 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Baseline | 36.45 Celsius (C) | Standard Deviation 0.38 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 1 Day 1 | 0.04 Celsius (C) | Standard Deviation 0.36 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 1 Day 15 | -0.01 Celsius (C) | Standard Deviation 0.43 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 2 Day 1 | -0.04 Celsius (C) | Standard Deviation 0.52 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 2 Day 15 | -0.12 Celsius (C) | Standard Deviation 0.47 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 4 Day 1 | -0.08 Celsius (C) | Standard Deviation 0.38 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Day of Surgery | -0.01 Celsius (C) | Standard Deviation 0.38 |
| Anastrozole + Palbociclib | Change From Baseline in Body Temperature Over Time | Change from Baseline at Cycle 3 Day 1 | 0.01 Celsius (C) | Standard Deviation 0.39 |
Secondary
Change From Baseline in Diastolic Blood Pressure Over Time
Diastolic blood pressure was measured while the participant was in a seated position.
Time frame: Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 1 | -2.42 mmHg | Standard Deviation 7.77 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 3 Day 1 | -5.25 mmHg | Standard Deviation 8.51 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 1 | -4.79 mmHg | Standard Deviation 10.08 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 4 Day 1 | -4.35 mmHg | Standard Deviation 9.31 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 15 | -4.80 mmHg | Standard Deviation 8.58 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Day of Surgery | -4.93 mmHg | Standard Deviation 8.72 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 15 | -5.64 mmHg | Standard Deviation 9.24 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at End of Study | -2.73 mmHg | Standard Deviation 8.37 |
| Giredestrant + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Baseline | 80.40 mmHg | Standard Deviation 8.84 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at End of Study | -2.52 mmHg | Standard Deviation 12.11 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Baseline | 78.49 mmHg | Standard Deviation 9.55 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 1 | 0.39 mmHg | Standard Deviation 8.13 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 15 | -2.42 mmHg | Standard Deviation 8.71 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 1 | -0.76 mmHg | Standard Deviation 8.8 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 15 | -1.32 mmHg | Standard Deviation 9.64 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 3 Day 1 | -0.16 mmHg | Standard Deviation 9.52 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Cycle 4 Day 1 | -2.57 mmHg | Standard Deviation 9.5 |
| Anastrozole + Palbociclib | Change From Baseline in Diastolic Blood Pressure Over Time | Change from Baseline at Day of Surgery | -2.15 mmHg | Standard Deviation 9.58 |
Secondary
Change From Baseline in Pulse Rate Over Time
Pulse rate was measured while the participant was in a seated position.
Time frame: Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 1 Day 1 | -4.74 beats/min | Standard Deviation 9.07 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 3 Day 1 | -5.47 beats/min | Standard Deviation 11.61 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 2 Day 1 | -5.20 beats/min | Standard Deviation 10.26 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 4 Day 1 | -5.67 beats/min | Standard Deviation 9.79 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 1 Day 15 | -6.02 beats/min | Standard Deviation 12.02 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Day of Surgery | -4.14 beats/min | Standard Deviation 11.25 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 2 Day 15 | -7.68 beats/min | Standard Deviation 11.03 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at End of Study | -0.61 beats/min | Standard Deviation 10.74 |
| Giredestrant + Palbociclib | Change From Baseline in Pulse Rate Over Time | Baseline | 75.86 beats/min | Standard Deviation 10.67 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at End of Study | 1.59 beats/min | Standard Deviation 10.44 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Baseline | 76.73 beats/min | Standard Deviation 9.85 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 1 Day 1 | -1.96 beats/min | Standard Deviation 9.43 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 1 Day 15 | -1.47 beats/min | Standard Deviation 8.15 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 2 Day 1 | -1.11 beats/min | Standard Deviation 10.79 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 2 Day 15 | -1.95 beats/min | Standard Deviation 8.64 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 3 Day 1 | -0.81 beats/min | Standard Deviation 10.83 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Cycle 4 Day 1 | -1.11 beats/min | Standard Deviation 10.62 |
| Anastrozole + Palbociclib | Change From Baseline in Pulse Rate Over Time | Change from Baseline at Day of Surgery | -1.26 beats/min | Standard Deviation 10.46 |
Secondary
Change From Baseline in Respiratory Rate Over Time
Respiratory rate was measured while the participant was in a seated position.
Time frame: Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 1 Day 1 | 0.30 breath/minute (min) | Standard Deviation 2.12 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 3 Day 1 | 0.07 breath/minute (min) | Standard Deviation 1.58 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 2 Day 1 | -0.10 breath/minute (min) | Standard Deviation 1.83 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 4 Day 1 | -0.04 breath/minute (min) | Standard Deviation 1.71 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 1 Day 15 | -0.01 breath/minute (min) | Standard Deviation 1.49 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Day of Surgery | 0.04 breath/minute (min) | Standard Deviation 1.72 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 2 Day 15 | -0.24 breath/minute (min) | Standard Deviation 1.71 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at End of Study | -0.26 breath/minute (min) | Standard Deviation 1.65 |
| Giredestrant + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Baseline | 17.16 breath/minute (min) | Standard Deviation 2.27 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at End of Study | 0.01 breath/minute (min) | Standard Deviation 1.42 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Baseline | 17.10 breath/minute (min) | Standard Deviation 2.05 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 1 Day 1 | 0.26 breath/minute (min) | Standard Deviation 1.5 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 1 Day 15 | -0.06 breath/minute (min) | Standard Deviation 1.36 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 2 Day 1 | 0.16 breath/minute (min) | Standard Deviation 1.34 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 2 Day 15 | -0.03 breath/minute (min) | Standard Deviation 1.64 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 3 Day 1 | 0.01 breath/minute (min) | Standard Deviation 1.61 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Cycle 4 Day 1 | 0.01 breath/minute (min) | Standard Deviation 1.53 |
| Anastrozole + Palbociclib | Change From Baseline in Respiratory Rate Over Time | Change from Baseline at Day of Surgery | -0.02 breath/minute (min) | Standard Deviation 1.69 |
Secondary
Change From Baseline in Systolic Blood Pressure Over Time
Systolic blood pressure was measured while the participant was in a seated position.
Time frame: Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 1 | -0.82 millimeters of mercury (mmHg) | Standard Deviation 11.11 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 3 Day 1 | -2.66 millimeters of mercury (mmHg) | Standard Deviation 16.95 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 1 | -2.08 millimeters of mercury (mmHg) | Standard Deviation 14.13 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 4 Day 1 | -1.29 millimeters of mercury (mmHg) | Standard Deviation 15.3 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 15 | -2.55 millimeters of mercury (mmHg) | Standard Deviation 14.01 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Day of Surgery | -2.35 millimeters of mercury (mmHg) | Standard Deviation 13.79 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 15 | -4.25 millimeters of mercury (mmHg) | Standard Deviation 15.37 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at End of Study | -5.38 millimeters of mercury (mmHg) | Standard Deviation 13.98 |
| Giredestrant + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Baseline | 135.63 millimeters of mercury (mmHg) | Standard Deviation 14.13 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at End of Study | -1.67 millimeters of mercury (mmHg) | Standard Deviation 16.2 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Baseline | 130.03 millimeters of mercury (mmHg) | Standard Deviation 16.43 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 1 | 1.12 millimeters of mercury (mmHg) | Standard Deviation 13.65 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 1 Day 15 | 0.23 millimeters of mercury (mmHg) | Standard Deviation 15.85 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 1 | 0.28 millimeters of mercury (mmHg) | Standard Deviation 14.43 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 2 Day 15 | 0.16 millimeters of mercury (mmHg) | Standard Deviation 16.49 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 3 Day 1 | 0.33 millimeters of mercury (mmHg) | Standard Deviation 15.81 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Cycle 4 Day 1 | -0.25 millimeters of mercury (mmHg) | Standard Deviation 14.17 |
| Anastrozole + Palbociclib | Change From Baseline in Systolic Blood Pressure Over Time | Change from Baseline at Day of Surgery | 1.51 millimeters of mercury (mmHg) | Standard Deviation 15.24 |
Secondary
Complete Cell Cycle Arrest (CCCA) Rate at Week 2
CCCA was defined as the percentage of participants with centrally assessed Ki67 scores ≤2.7%. The CCCA rate at Week 2 was summarized.
Time frame: Week 2
Population: Efficacy-evaluable population included participants with Ki67-evaluable tumor specimens at baseline and Week 2. Participants with missing central Ki67 scores at baseline and/or Week 2 were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Giredestrant + Palbociclib | Complete Cell Cycle Arrest (CCCA) Rate at Week 2 | 19.6 percentage of participants |
| Anastrozole + Palbociclib | Complete Cell Cycle Arrest (CCCA) Rate at Week 2 | 12.8 percentage of participants |
95% CI: [-4.25, 17.97]
Secondary
Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
AE is any untoward medical occurrence in clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign, symptom/disease temporally associated with use of a medicinal product, whether or not related to medicinal product. Preexisting conditions which worsen during a study also considered as AEs. Severity of AEs was determined per NCI CTCAE v5.0. Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care activities of daily living; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE.
Time frame: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Giredestrant + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AEs | 104 Participants |
| Giredestrant + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 | 19 Participants |
| Giredestrant + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 | 35 Participants |
| Giredestrant + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 3 | 45 Participants |
| Giredestrant + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 4 | 4 Participants |
| Giredestrant + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 5 | 1 Participants |
| Anastrozole + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 4 | 2 Participants |
| Anastrozole + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AEs | 98 Participants |
| Anastrozole + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 3 | 45 Participants |
| Anastrozole + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 | 20 Participants |
| Anastrozole + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 5 | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 | 31 Participants |
Secondary
Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline
Blood chemistry parameters were measured per NCI CTCAE v5.0. Grade 0=normal, and Grades 1 to 4 represent worsening levels of parameter outside of normal range in the specified direction of abnormality (high & low are above & below the range, respectively). Number of participants with shift in blood chemistry values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. Marked reference range for albumin 32-45 grams per liter (g/L), alkaline phosphatase 20-130 units per liter (U/L), serum glutamic pyruvic transaminase (SGPT)/ alanine transaminase (ALT) 4-36 U/L, serum glutamic oxaloacetic transaminase (SGOT)/ aspartate transaminase (AST) 8-33 U/L, calcium 2.3-2.74 millimoles per liter (mmol/L), cholesterol 3.88-6.47mmol/L, creatinine 6-12 milligrams per liter (mg/L), glucose 3.9-6.1 mmol/L, potassium 3.5-5.0 mmol/L, sodium 135-147 mmol/L, bilirubin 2-21 micromoles per liter (μmol/L), triglycerides 0.11-2.15 mmol/L, & uric acid 2.7-7.3 milligrams per deciliter (mg/dL).
Time frame: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Participants with at least 1 post-baseline assessment were included in the analysis. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Albumin: low | 1 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Alkaline Phosphatase: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | SGPT/ALT: High | 1 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | SGOT/AST: High | 1 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Calcium: Low | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Calcium: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Cholesterol: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Creatinine: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Glucose: Low | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Potassium: Low | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Potassium: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Sodium: Low | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Sodium: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Bilirubin: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Triglycerides: High | 1 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Uric Acid: High | 21 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Uric Acid: High | 22 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Albumin: low | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Glucose: Low | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Alkaline Phosphatase: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Sodium: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | SGPT/ALT: High | 5 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Potassium: Low | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | SGOT/AST: High | 3 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Triglycerides: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Calcium: Low | 3 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Potassium: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Calcium: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Bilirubin: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Cholesterol: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Sodium: Low | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Creatinine: High | 1 Participants |
Secondary
Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline
Hematology test parameters were measured per NCI CTCAE v5.0. Grade 0 is normal, and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Number of participants with shift in the hematology values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. A marked reference range for hemoglobin 12.3-15.3 grams per deciliter (g/dL), lymphocytes absolute (Abs) 1.0-4.8 10\^3/microliters (uL), neutrophils total, Abs, 1.8-8.5 10\^3/uL, platelet 100-450 10\^9/liter (L), total leukocyte 4.4-11 10\^9/L.
Time frame: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Population: Safety-evaluable population included all participants who received any amount of study treatment. Participants with at least 1 post-baseline assessment were included in the analysis. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Hemoglobin: Low | 3 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Hemoglobin: High | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Lymphocytes Abs: Low | 9 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Lymphocytes Abs: High | 1 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Neutrophils, Total, Abs: Low | 43 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Platelet: Low | 0 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Total Leukocyte Count: Low | 15 Participants |
| Giredestrant + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Total Leukocyte Count: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Total Leukocyte Count: High | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Hemoglobin: Low | 1 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Neutrophils, Total, Abs: Low | 38 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Hemoglobin: High | 1 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Total Leukocyte Count: Low | 11 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Lymphocytes Abs: Low | 2 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Platelet: Low | 0 Participants |
| Anastrozole + Palbociclib | Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline | Lymphocytes Abs: High | 2 Participants |
Secondary
Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR), as determined by the investigator according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Ultrasound and clinical exam were used to assess response. CR per mRECIST was defined as the disappearance of all target lesions. PR per mRECIST was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. An estimate of ORR and its 95% confidence interval (CI) was calculated using the Clopper-Pearson method.
Time frame: Baseline up to Cycle 4 Day 1 (each cycle is 28 days)
Population: ORR-evaluable population included all randomized participants with measurable disease at baseline. Participants not meeting the criteria for ORR, including participants without any post-baseline tumor assessment, were considered as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Giredestrant + Palbociclib | Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator | 50.0 percentage of participants |
| Anastrozole + Palbociclib | Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator | 49.1 percentage of participants |
Comparison: ORR was calculated using the stratified Cochran-Mantel-Haenszel test.p-value: 0.827295% CI: [-14.66, 12.81]Cochran-Mantel-Haenszel
Secondary
Plasma Concentration of Giredestrant at Specified Timepoints
Time frame: Window of Opportunity Phase: Day 1 (3 hours Postdose) and Day 15 (Predose) during Cycle 0 (the 15-day period in Window of Opportunity Phase is called Cycle 0 for PK analysis); Neoadjuvant Phase: Cycle 2 Day 1, Predose
Population: Pharmacokinetics (PK) evaluable population included all participants who received giredestrant and had at least one evaluable post-dose giredestrant plasma concentration. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Giredestrant + Palbociclib | Plasma Concentration of Giredestrant at Specified Timepoints | Window of Opportunity Phase: Cycle 0 Day 1, 3-h Postdose | 81.8 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 284 |
| Giredestrant + Palbociclib | Plasma Concentration of Giredestrant at Specified Timepoints | Window of Opportunity Phase: Cycle 0 Day 15, Predose | 137 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 61.1 |
| Giredestrant + Palbociclib | Plasma Concentration of Giredestrant at Specified Timepoints | Neoadjuvant Phase: Cycle 2 Day 1, Predose | 130 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 122 |