Breast Neoplasms
Conditions
Brief summary
A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic complete response rate when compared to the historical control of single agent aromatase inhibitors, 2) result in fewer patients with on therapy Ki67\>10% compared to historical control.
Interventions
DRUGPD0332991
DRUGAnastrozole
DRUGGoserelin
PROCEDURESurgery (standard of care)
-Breast and axillary lymph node surgery
PROCEDURETumor biopsy
Sponsors
Pfizer
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-registration PIK3CA Mutant Inclusion * Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible * Female ≥18 years of age * ECOG performance status of 0, 1 or 2 * Life expectancy \> 4 months * Premenopausal, patient must be willing to comply with pregnancy requirements * Adequate organ and marrow function * leukocytes ≥ 3,000/mcL * absolute neutrophil count ≥ 1,500/mcL * platelets ≥ 100,000/mcL * total bilirubin ≤ ULN * AST(SGOT)/ and ALT(SGPT) \< 2.5 X ULN * Creatinine ≤ ULN * Able to understand and willing to sign an IRB-approved written informed consent document Exclusion * Prior treatment of this cancer including: surgery, radiation, chemotherapy, biotherapy, hormonal therapy, investigational agent prior to study entry * Receiving any investigational agents * Prior therapy with any Cdk4 inhibitor * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism * Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements * Pregnant/nursing * Unwilling to employ adequate contraception * Known HIV-positive on combination antiretroviral therapy * Evidence of inflammatory cancer * Known metastatic disease * Current use of anticoagulation therapy * Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy * Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study * Corrected QT interval \>470 msec Registration PIK3CA Mutant Inclusion The criteria below must be met in addition to the pre-registration criteria, except treatment with endocrine therapy for this cancer is allowed prior to registration * PIK3CA mutant cohort: tumor PIK3CA mutation present * Premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration
Exclusion criteria
below must be met in addition to the pre-registration criteria -Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort) PIK3CA Wild Type Inclusion * Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible * For the PIK3CA wild type cohort: tumor PIK3CA mutation absent. Note that if a patient did not have sufficient research tissue for PIK3CA sequencing at pre-registration or if PIK3CA sequencing result is delayed, she could be registered and enrolled on the PD991 trial without assigning to a particular cohort at the time of enrollment. PIK3CA sequencing will be performed in the future on tumors collected at subsequent time points to assign the treatment cohort or when the PIK3CA sequencing data is available * For the endocrine resistant cohort: Ki67 \> 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. Note that prior neoadjuvant endocrine therapy could include any endocrine therapy (including aromatase inhibitor, tamoxifen, fulvestrant) alone or in combination, or endocrine therapy in combination with any investigational agent that is not a Cdk 4/6 inhibitor \*Patients who had a Day 17 Ki67 \> 10% from the NCI9170 trial are eligible for the endocrine resistant cohort * Female \>18 years of age * ECOG performance status of 0, 1 or 2 * Life expectancy \> 4 months * If premenopausal, patient must be willing to comply with pregnancy requirements * Adequate organ and marrow function: * leukocytes ≥ 3,000/mcL * absolute neutrophil count ≥ 1,500/mcL * platelets ≥ 100,000/mcL * total bilirubin ≤ ULN * AST(SGOT)/ and ALT(SGPT) \< 2.5 X ULN * Creatinine ≤ ULN * In premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration. * Able to understand and willing to sign an IRB-approved written informed consent document Exclusion * Prior treatment of this cancer including: Surgery, Radiation therapy, Chemotherapy, Biotherapy, Hormonal therapy, Investigational agent prior to study entry * Receiving any other investigational agents * Prior therapy with any Cdk4 inhibitor * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism * Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements * Pregnant/nursing * Unwilling to employ adequate contraception * Known HIV-positive on combination antiretroviral therapy * Evidence of inflammatory cancer * Known metastatic disease * Current use of anticoagulation therapy * Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy * Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study * Corrected QT interval \>470 msec * Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort) Endocrine Resistant Inclusion * Clinical T2-T4c at diagnosis or screening, any N, M0 invasive ER+ (Allred Score at least 3 or \> 1% ER positivity) and HER2 negative (0 or 1+ by IHC or FISH negative or equivocal) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive breast cancer that is ER pos, HER2 neg or equivocal or DCIS in the contralateral breast are eligible; multi-focal diseases are not excluded. The dominant lesion will be followed per protocol * Ki67 \> 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. If Ki67 is \> 10% by local testing, the Ki67 slide and H&E slide need to be reviewed by the study pathologist to confirm eligibility (discuss with Study Chair). For patients external to Washington University, please contact the Washington University coordinator by email so that a screening ID# can be assigned prior to shipment of the slides * Female ≥ 18 years of age * ECOG performance status of 0, 1 or 2 * Pre- or post-menopausal women are eligible. If premenopausal, patient must be willing to comply with pregnancy requirements and agrees with GnRH agonist therapy for ovarian suppression during the study * Adequate organ and marrow function: * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Total bilirubin ≤ ULN * AST(SGOT)/ and ALT(SGPT) \< 2.5 X ULN * Creatinine ≤ ULN * Able to understand and willing to sign an IRB-approved written informed consent document Exclusion * Prior treatment of this cancer including: Surgery, Radiation, Chemotherapy * Receiving any other investigational agents * Prior therapy with Cdk4 inhibitor * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism * Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements * Pregnant/nursing * Unwilling to employ adequate contraception * Known HIV-positive on combination antiretroviral therapy * Known metastatic disease * Current use of anticoagulation therapy * Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy * Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study * Corrected QT interval \>470 msec * Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort) Adjuvant Inclusion * Derived benefit from PD 0332991 in the neoadjuvant setting in this trial. This includes the 26 patients who achieved complete cell cycle arrest only after the addition of PD 0332991 (C1D1 Ki67 \>2.7% and C1D15 Ki67 ≤ 2.7%) from the main study (PIK3CA WT, mutant, or unknown cohorts) as well as any patients who have a Ki67 ≤ 10% on C1D15 biopsy in the endocrine resistant cohort * ECOG performance status of 0, 1 or 2 * Premenopausal, patient must be willing to comply with pregnancy requirements laid out * Adequate organ and marrow function * leukocytes ≥ 3,000/mcL * absolute neutrophil count ≥ 1,500/mcL * platelets ≥ 100,000/mcL * total bilirubin ≤ ULN * AST(SGOT)/ and ALT(SGPT) ≤ 2.5 X ULN * Creatinine ≤ ULN * Underwent surgery of the breast and axilla for curative intent * At least 4 weeks post completion of adjuvant chemotherapy and radiation therapy if indicated * Patients who already started on adjuvant hormonal therapy are eligible under the following conditions: * For the 26 patients who enrolled in the initial cohorts and derived benefit from neoadjuvant PD 0332991 (C1D1 Ki67 \>2.7% and C1D15 Ki67 ≤ 2.7%), adjuvant PD 0332991 should be initiated as soon as possible if adjuvant hormonal therapy has been initiated and the patient has completed radiation if indicated * For patients who enrolled in the endocrine resistant cohort and derived benefit from neoadjuvant PD 0332991 (C1D15 Ki67 ≤ 10%), adjuvant PD 0332991 should be initiated within 6 months or sooner after initation of adjuvant hormonal therapy * Able to understand and willing to sign an IRB-approved written informed consent document Exclusion * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism * Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, ssychiatric illness/social situations that would limit compliance with study requirements * Pregnant/nursing * Unwilling to employ adequate contraception * Known HIV-positive on combination antiretroviral therapy. -Known metastatic disease * Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study * Corrected QT interval \>470 msec * Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only) | At cycle 1 day 15 (2 weeks) | Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991 |
| Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only) | At cycle 1 day 15 (2 weeks) | Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only) | At cycle 1 day 15 (2 weeks) | Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991 |
| Number of Participants With Complete Cell Cycle Arrest | Cycle 1 day 1 and cycle 1 day 15 (2 weeks) | Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15 |
| Clinical Response Rate | 16 weeks | * The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment. * Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions. * Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion. |
| Radiologic Response Rate | At the end of cycle 4 prior to surgery (estimated to be 16 weeks) | * The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy. * Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions. * Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion. |
| Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy | The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration. |
| Number of Participants With a PEPI-0 Score | At the time of surgery (estimated to be 5 months) | * Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as T below), lymph node status (indicated as N below), and estrogen receptor (ER) level (indicated as ER Allred below). * PEPI-0 score indicates T1 or T2, N0, Ki67 \< 2.7%, ER Allred \> 2. * It predicts a low risk of recurrence. |
| Change in Ki67 Level of Tumor Specimens | Pre-treatment and cycle 1 day 15 | To assess Ki67 level on serially collected tumor specimens |
| Distant Recurrence Rate | 5 years | Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis. |
| Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years) | The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration. |
| Overall Survival | 5 years | — |
| Relapse-free Survival | 5 years | — |
| Local Recurrence Rate | 5 years | Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall. |
| Regional Recurrence Rate | 5 years | Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla. |
| Rate of Second Primary Cancer (Non-breast) | 5 years | Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible. |
| Number of Participants With Pathologic Complete Response (pCR) | At the time of surgery (estimated to be 5 months) | -A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes. |
| Rate of Second Primary Breast Cancer | 5 years | Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: PIK3CA Wild Type Cohort * Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
* Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
* Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
* Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
* Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned. | 34 |
| Arm 2: PIK3CA Mutant Type Cohort * Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
* Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
* Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
* Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
* Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned. | 16 |
| Arm 3: Endocrine Resistant Cohort * Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
* Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
* Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
* Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned. | 34 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Neoadjuvant | Adverse Event | 0 | 1 | 2 | 0 |
| Neoadjuvant | Disease progression | 0 | 1 | 1 | 0 |
| Neoadjuvant | High estradiol | 0 | 1 | 0 | 0 |
| Neoadjuvant | Ki67 > 10% | 4 | 0 | 10 | 0 |
| Neoadjuvant | Withdrawal by Subject | 3 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1: PIK3CA Wild Type Cohort | Total | Arm 3: Endocrine Resistant Cohort | Arm 2: PIK3CA Mutant Type Cohort |
|---|---|---|---|---|
| Age, Continuous | 58 years | 55.5 years | 53 years | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 5 Participants | 5 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 77 Participants | 28 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 70 Participants | 24 Participants | 16 Participants |
| Region of Enrollment United States | 34 participants | 84 participants | 34 participants | 16 participants |
| Sex: Female, Male Female | 34 Participants | 84 Participants | 34 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 16 | 4 / 34 | 0 / 7 |
| other Total, other adverse events | 34 / 34 | 16 / 16 | 34 / 34 | 7 / 7 |
| serious Total, serious adverse events | 2 / 34 | 1 / 16 | 1 / 34 | 1 / 7 |
Outcome results
Primary
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)
Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
Time frame: At cycle 1 day 15 (2 weeks)
Population: Arm 1 and Arm 2 participants were not evaluable for this outcome measure as it is for Arm 3: Endocrine Resistant Cohort only. 1 participant was not evaluable for this outcome measure as the participant did not have any tissue available at the cycle 1 day 15 biopsy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 3: Endocrine Resistant Cohort | Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only) | 19 Participants |
Primary
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)
Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
Time frame: At cycle 1 day 15 (2 weeks)
Population: Arm 2 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 1: PIK3CA Wild Type Cohort only. 5 participants in Arm 1 were not evaluable. 1 participant was not evaluable due to insufficient quality of specimen, 1 participant was not evaluable because she withdrew prior to starting treatment, 2 participants were not evaluable because there was no tumor present on biopsy, and 1 participant was not evaluable because she withdrew prior to cycle 1 day 15 biopsy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only) | 23 Participants |
Secondary
Change in Ki67 Level of Tumor Specimens
To assess Ki67 level on serially collected tumor specimens
Time frame: Pre-treatment and cycle 1 day 15
Population: Only participants who had tissue available at the two time points were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Change in Ki67 Level of Tumor Specimens | Cycle 1 Day 15 | 8.18 percentage of Ki67 in tumor sample |
| Arm 1: PIK3CA Wild Type Cohort | Change in Ki67 Level of Tumor Specimens | Pre-treatment | 29.75 percentage of Ki67 in tumor sample |
| Arm 2: PIK3CA Mutant Type Cohort | Change in Ki67 Level of Tumor Specimens | Cycle 1 Day 15 | 0.51 percentage of Ki67 in tumor sample |
| Arm 2: PIK3CA Mutant Type Cohort | Change in Ki67 Level of Tumor Specimens | Pre-treatment | 19.76 percentage of Ki67 in tumor sample |
| Arm 3: Endocrine Resistant Cohort | Change in Ki67 Level of Tumor Specimens | Pre-treatment | 33.52 percentage of Ki67 in tumor sample |
| Arm 3: Endocrine Resistant Cohort | Change in Ki67 Level of Tumor Specimens | Cycle 1 Day 15 | 15.27 percentage of Ki67 in tumor sample |
Secondary
Change in Ki67 Level of Tumor Specimens
To assess Ki67 level on serially collected tumor specimens
Time frame: Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days)
Population: Only participants who had tissue available at the two time points were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Change in Ki67 Level of Tumor Specimens | Cycle 1 Day 15 | 11.70 percentage of Ki67 in tumor sample |
| Arm 1: PIK3CA Wild Type Cohort | Change in Ki67 Level of Tumor Specimens | At time of surgery | 23.00 percentage of Ki67 in tumor sample |
| Arm 2: PIK3CA Mutant Type Cohort | Change in Ki67 Level of Tumor Specimens | Cycle 1 Day 15 | 0.51 percentage of Ki67 in tumor sample |
| Arm 2: PIK3CA Mutant Type Cohort | Change in Ki67 Level of Tumor Specimens | At time of surgery | 8.75 percentage of Ki67 in tumor sample |
| Arm 3: Endocrine Resistant Cohort | Change in Ki67 Level of Tumor Specimens | Cycle 1 Day 15 | 0.97 percentage of Ki67 in tumor sample |
| Arm 3: Endocrine Resistant Cohort | Change in Ki67 Level of Tumor Specimens | At time of surgery | 2.84 percentage of Ki67 in tumor sample |
Secondary
Clinical Response Rate
* The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment. * Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions. * Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.
Time frame: 16 weeks
Population: 7 participants in Arm 1 were not evaluable for this outcome measure. 3 participants in Arm 2 were not evaluable for this outcome measure. 12 participants in Arm 3 were not evaluable for this outcome measure. Reasons include patient withdrawal (n=4), progressive disease during cycle 1 (n=2), cycle 1 day 15 Ki67 \>10% (n=14) high estradiol (n=1), and adverse event (n=1).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Clinical Response Rate | 21 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Clinical Response Rate | 10 Participants |
| Arm 3: Endocrine Resistant Cohort | Clinical Response Rate | 16 Participants |
Secondary
Distant Recurrence Rate
Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis.
Time frame: 5 years
Secondary
Local Recurrence Rate
Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall.
Time frame: 5 years
Secondary
Number of Participants With a PEPI-0 Score
* Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as T below), lymph node status (indicated as N below), and estrogen receptor (ER) level (indicated as ER Allred below). * PEPI-0 score indicates T1 or T2, N0, Ki67 \< 2.7%, ER Allred \> 2. * It predicts a low risk of recurrence.
Time frame: At the time of surgery (estimated to be 5 months)
Population: Some participants were not evaluable for this outcome measure due to participant withdrawal and surgery not completed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Number of Participants With a PEPI-0 Score | 3 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Number of Participants With a PEPI-0 Score | 2 Participants |
| Arm 3: Endocrine Resistant Cohort | Number of Participants With a PEPI-0 Score | 1 Participants |
Secondary
Number of Participants With Complete Cell Cycle Arrest
Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15
Time frame: Cycle 1 day 1 and cycle 1 day 15 (2 weeks)
Population: PIK3CA Wild Type Cohort - 5 participants not evaluable. 1 due to insufficient quality of specimen, 1 because she withdrew prior to starting treatment, 2 participants because there was no tumor present on biopsy, and 1 because she withdrew prior to cycle 1 day 15 biopsy. Endocrine Resistant Cohort-1 participant because no tissue available at the cycle 1 day 15 biopsy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Number of Participants With Complete Cell Cycle Arrest | Cycle 1 Day 1 complete cell cycle arrest | 8 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Number of Participants With Complete Cell Cycle Arrest | Cycle 1 Day 15 complete cell cycle arrest | 23 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Number of Participants With Complete Cell Cycle Arrest | Cycle 1 Day 1 complete cell cycle arrest | 4 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Number of Participants With Complete Cell Cycle Arrest | Cycle 1 Day 15 complete cell cycle arrest | 16 Participants |
| Arm 3: Endocrine Resistant Cohort | Number of Participants With Complete Cell Cycle Arrest | Cycle 1 Day 1 complete cell cycle arrest | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Number of Participants With Complete Cell Cycle Arrest | Cycle 1 Day 15 complete cell cycle arrest | 19 Participants |
Secondary
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)
Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
Time frame: At cycle 1 day 15 (2 weeks)
Population: Arm 1 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 2: PIK3CA Mutant Type Cohort only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 2: PIK3CA Mutant Type Cohort | Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only) | 16 Participants |
Secondary
Number of Participants With Pathologic Complete Response (pCR)
-A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.
Time frame: At the time of surgery (estimated to be 5 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Number of Participants With Pathologic Complete Response (pCR) | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Number of Participants With Pathologic Complete Response (pCR) | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Number of Participants With Pathologic Complete Response (pCR) | 0 Participants |
Secondary
Overall Survival
Time frame: 5 years
Secondary
Radiologic Response Rate
* The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy. * Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions. * Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.
Time frame: At the end of cycle 4 prior to surgery (estimated to be 16 weeks)
Population: Arm 1 PIK3CA Wild Type Cohort: 23 participants not evaluable due to imaging not being performed. Arm 2 PIK3CA Mutant Type Cohort: 9 participants not evaluable due to imaging not being performed. Arm 3 Endocrine Resistant Cohort: 10 participants not evaluable due to imaging not being performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Radiologic Response Rate | 7 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Radiologic Response Rate | 3 Participants |
| Arm 3: Endocrine Resistant Cohort | Radiologic Response Rate | 6 Participants |
Secondary
Rate of Second Primary Breast Cancer
Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.
Time frame: 5 years
Secondary
Rate of Second Primary Cancer (Non-breast)
Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible.
Time frame: 5 years
Secondary
Regional Recurrence Rate
Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla.
Time frame: 5 years
Secondary
Relapse-free Survival
Time frame: 5 years
Secondary
Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events
The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.
Time frame: From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dysgeusia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pain | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 constipation | 4 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 postnasal drip | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 shingles | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 rectal pain | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry mouth | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 sinusitis | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 edema limbs | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 sore throat | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 urinary tract infection | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pelvic pain | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 white blood cell decreased | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 seroma | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry eye | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dyspepsia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 alanine aminotransferase increased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 alopecia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 vomiting | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 alanine aminotransferase increased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 allergic rhinitis | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 peripheral sensory neuropathy | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 aspartate aminotransferase increased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry skin | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 flatulence | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 aspartate aminotransferase increased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 confusion | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fatigue | 15 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 lymphocyte count decreased | 3 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 memory impairment | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 papulopustular rash | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 neutrophil count decreased | 14 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 cough | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 gastroesophageal reflux disease | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 neutrophil count decreased | 7 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 headache | 5 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pruritus | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 platelet count decreased | 6 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 stomatitis | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hyperhidrosis | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 weight loss | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fever | 3 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 gastrointestinal pain | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 rash maculo-papular | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dyspnea | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 anorexia | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 depression | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hypocalcemia | 3 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 rash maculo-papular | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 mucositis oral | 9 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hypokalemia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 chills | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 diarrhea | 4 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hyponatremia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fever blister | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 anemia | 4 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 arthralgia | 5 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 epistaxis | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 nausea | 8 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 back pain | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 localized edema | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 itching | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 bone pain | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 peripheral motor neuropathy | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 insomnia | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 myalgia | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hot flashes | 10 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 osteoporosis | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 nasal congestion | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 oral pain | 0 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dizziness | 3 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 white blood cell decreased | 23 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dizziness | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dysgeusia | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 anorexia | 3 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 memory impairment | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 rectal pain | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 cough | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 peripheral motor neuropathy | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 peripheral sensory neuropathy | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 confusion | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 stomatitis | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 insomnia | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry eye | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pelvic pain | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 allergic rhinitis | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 vomiting | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 white blood cell decreased | 6 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dyspnea | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 epistaxis | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 chills | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 nasal congestion | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 postnasal drip | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 sore throat | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 edema limbs | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 alopecia | 4 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 constipation | 3 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry skin | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fatigue | 8 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 papulopustular rash | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pruritus | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 rash maculo-papular | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fever | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 rash maculo-papular | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fever blister | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 itching | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 localized edema | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hot flashes | 7 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 diarrhea | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pain | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 headache | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 shingles | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 sinusitis | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry mouth | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 urinary tract infection | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 seroma | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 alanine aminotransferase increased | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dyspepsia | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 alanine aminotransferase increased | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 aspartate aminotransferase increased | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 aspartate aminotransferase increased | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 flatulence | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 lymphocyte count decreased | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 depression | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 neutrophil count decreased | 4 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 neutrophil count decreased | 6 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 gastroesophageal reflux disease | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 platelet count decreased | 5 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 weight loss | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 white blood cell decreased | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 gastrointestinal pain | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hyperhidrosis | 2 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hypocalcemia | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hypokalemia | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 mucositis oral | 3 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hyponatremia | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 arthralgia | 4 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 back pain | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 nausea | 3 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 bone pain | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 anemia | 5 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 myalgia | 0 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 osteoporosis | 1 Participants |
| Arm 2: PIK3CA Mutant Type Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 oral pain | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hot flashes | 3 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 white blood cell decreased | 11 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 myalgia | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 peripheral motor neuropathy | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 anemia | 7 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry eye | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 constipation | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 diarrhea | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry mouth | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dyspepsia | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 flatulence | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 gastroesophageal reflux disease | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 gastrointestinal pain | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 mucositis oral | 3 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 nausea | 10 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 oral pain | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 rectal pain | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 stomatitis | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 vomiting | 2 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 chills | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 edema limbs | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fatigue | 6 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fever | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 localized edema | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pain | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 shingles | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 sinusitis | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 urinary tract infection | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 seroma | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 alanine aminotransferase increased | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 alanine aminotransferase increased | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 aspartate aminotransferase increased | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 aspartate aminotransferase increased | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 lymphocyte count decreased | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 neutrophil count decreased | 12 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 neutrophil count decreased | 13 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 platelet count decreased | 3 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 weight loss | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 white blood cell decreased | 2 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 anorexia | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hypocalcemia | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hypokalemia | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hyponatremia | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 arthralgia | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 back pain | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 bone pain | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 osteoporosis | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dizziness | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dysgeusia | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 headache | 2 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 memory impairment | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 peripheral sensory neuropathy | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 confusion | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 depression | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 insomnia | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pelvic pain | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 allergic rhinitis | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 cough | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dyspnea | 2 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 epistaxis | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 nasal congestion | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 postnasal drip | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 sore throat | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 alopecia | 2 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 dry skin | 1 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 hyperhidrosis | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 papulopustular rash | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 pruritus | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 rash maculo-papular | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 3/4 rash maculo-papular | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 fever blister | 0 Participants |
| Arm 3: Endocrine Resistant Cohort | Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events | Grade 1/2 itching | 1 Participants |
Secondary
Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event
The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.
Time frame: From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 3/4 white blood cell count decreased | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 anemia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 blurred vision | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 watering eyes | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 diarrhea | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 gastritis | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 mucositis oral | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 nausea | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 vomiting | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 fatigue | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 upper respiratory infection | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 bruising | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 aspartate aminotransferase increased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 lymphocyte count decreased | 3 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 3/4 lymphocyte count decreased | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 neutrophil count decreased | 2 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 3/4 neutrophil count decreased | 3 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 platelet count decreased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 white blood cell count decreased | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 hyperglycemia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 arthralgia | 1 Participants |
| Arm 1: PIK3CA Wild Type Cohort | Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event | Grade 1/2 alopecia | 2 Participants |