Invasive Early Breast Cancer
Conditions
Keywords
Prospective, non-comparative, NIS, 600, postmenopausal, hormone-receptor, positive, EBC, tamoxifen, current medical practice.
Brief summary
The IES study (A5991012) investigated 4742 patients treated for 2 to 3 years with tamoxifen, who either continued the same treatment or switched to Aromasin® for a total treatment period of 5 years. Only 65 Romanian patients were enrolled in the IES study. It would therefore appear to be essential to evaluate and confirm the tolerability of Aromasin® and the ways in which it is used on a broader sample of patients and under the standard conditions of use as stipulated in the MA. This Non-Interventional study was designed to address these issues.
Detailed description
This is a prospective, non-comparative, non interventional study (NIS) in four hundred (400) postmenopausal women hormone-receptor positive invasive with early breast cancer, following 2-3 years of initial adjuvant tamoxifen therapy conducted in 60 sites from Romania according to protocol A5991091.The selection of patients based on diagnosis, the attribution of medicinal products and the follow-up of the subjects fall within the current medical practice. A Non-Interventional study is primarily observational in nature. The present Non-interventional Study is performed by medical oncologist and medical oncologist /radiation oncologist who agree to take part in this project. n/a The study was prematurely terminated on August 31th 2012 due to unexpected high rate of patient withdrawal caused by Aromasin reimbursement policy change in Romania; There were no safety issues related to study termination.
Interventions
DRUGAromasin
25 mg daily continuously
Sponsors
Pfizer
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Postmenopausal females, defined as one from the next : 1. Natural menopause \>/=1 year, 2. Surgical ovariectomy, 3. Chemotherapy-induced amenorrhoea \>/=2 years. * Patients who have had surgical treatment for histological confirmed breast cancer that was non-metastatic at the time of the initial diagnosis. * Patients who are disease-free after 2 or 3 years of adjuvant tamoxifen treatment. * Patients whose tumour was estrogen receptor positive (ER+). * Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
Exclusion criteria
* Patients for whom Aromasin® treatment is contraindicated (see SmPC). * Presence of metastasis or a contra lateral tumour. * Other adjuvant endocrine therapy. * Another concomitant antineoplastic treatment * Participation in a clinical trial with an investigational drug during the 30 days prior to enrolment in the study. * The patients are not supposed to participate to any other trial during all the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Baseline up to 28 days after last dose | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded using National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE,v4.0) as Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization; disabling; limiting self-care ADL); Grade 4 (Life-threatening; urgent intervention indicated) and Grade 5 (Death related to AE). |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug | Baseline up to 28 days after last dose | An AE (all causalities) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to exemestane was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy | Baseline up to Year 3 | — |
| Percentage of Participants Who Discontinued the Exemestane Therapy | Baseline up to Year 3 | — |
| Number of Missed Exemestane Doses | Week 25, 49, 73, 97, 121, 145 | — |
| Time to Disease Progression (TTP) | Baseline up to Year 3 | Time to disease progression was defined as the time from inclusion to first local or distant recurrence at any site. |
| Recurrence-free Survival (RFS) | Baseline up to Year 3 | Recurrence-free survival defined as the time from study inclusion to the first date of documented recurrence, with events defined as: local recurrence, distant recurrence, new primary breast cancer (includes both ipsilateral and contralateral second primaries), or death due to any cause. New primary cancer at sites other than the breast were not considered as recurrence. |
| Number of Participants With Reasons for Discontinuing Exemestane Therapy | Baseline up to Year 3 | — |
Countries
Romania
Participant flow
Recruitment details
All participants were recruited from Romania.
Participants by arm
| Arm | Count |
|---|---|
| Exemestane Participants with 2 to 3 years of initial adjuvant tamoxifen therapy received exemestane (Aromasin) 25 milligram (mg) tablet orally once daily as per local standard of care to complete 5 years of adjuvant hormonal therapy. | 378 |
| Total | 378 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 10 |
| Overall Study | Did not meet entrance criteria | 9 |
| Overall Study | Lack of Efficacy | 11 |
| Overall Study | Lost to Follow-up | 12 |
| Overall Study | Other | 58 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Protocol Violation | 33 |
| Overall Study | Study terminated by sponsor | 197 |
| Overall Study | Withdrawal by Subject | 16 |
Baseline characteristics
| Characteristic | Exemestane |
|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 9.6 |
| Number of Participants With Estrogen Receptor Positive | 378 participants |
| Number of Participants With Histopathological Grade Grade 1 | 62 participants |
| Number of Participants With Histopathological Grade Grade 2 | 178 participants |
| Number of Participants With Histopathological Grade Grade 3 | 65 participants |
| Number of Participants With Histopathological Grade Missing/No Response | 3 participants |
| Number of Participants With Histopathological Grade Unknown | 70 participants |
| Number of Participants With Lymph Node Involvement | NA participants |
| Number of Participants With Prior Chemotherapy | 0 participants |
| Number of Participants With Prior Radiation Therapy | 239 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Missing/No Response | 6 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Other | 2 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Stage I | 64 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Stage IIA | 129 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Stage IIB | 92 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Stage IIIA | 67 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Stage IIIB | 16 participants |
| Number of Participants With Tumor Node Metastasis (TNM) Stage Stage IIIC | 2 participants |
| Number of Participants With Type of Surgery Appendicectomy | 6 participants |
| Number of Participants With Type of Surgery Breast lump removal | 1 participants |
| Number of Participants With Type of Surgery Cataract operation | 1 participants |
| Number of Participants With Type of Surgery Cholecystectomy | 17 participants |
| Number of Participants With Type of Surgery Hysterectomy | 3 participants |
| Number of Participants With Type of Surgery Intervertebral disc operation | 1 participants |
| Number of Participants With Type of Surgery Malignant tumor excision | 1 participants |
| Number of Participants With Type of Surgery Salpingo-oophorectomy bilateral | 1 participants |
| Number of Participants With Type of Surgery Splenectomy | 1 participants |
| Number of Participants With Type of Tumor Ductal Carcinoma | 58 participants |
| Number of Participants With Type of Tumor Invasive Ductal Carcinoma | 246 participants |
| Number of Participants With Type of Tumor Invasive Lobular Carcinoma | 22 participants |
| Number of Participants With Type of Tumor Lobular Carcinoma | 4 participants |
| Number of Participants With Type of Tumor Medullary Carcinoma | 1 participants |
| Number of Participants With Type of Tumor Missing/No Response | 16 participants |
| Number of Participants With Type of Tumor Mucinous (Colloid) Carcinoma | 5 participants |
| Number of Participants With Type of Tumor Other | 24 participants |
| Number of Participants With Type of Tumor Papillary Carcinoma | 2 participants |
| Sex: Female, Male Female | 378 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 378 |
| serious Total, serious adverse events | 5 / 378 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded using National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE,v4.0) as Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization; disabling; limiting self-care ADL); Grade 4 (Life-threatening; urgent intervention indicated) and Grade 5 (Death related to AE).
Time frame: Baseline up to 28 days after last dose
Population: Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Grade 2 | 8 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Grade 1 | 6 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Grade 3 | 6 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Grade 4 | 2 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Grade 5 | 0 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity | Missing or Unknown | 2 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug
An AE (all causalities) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to exemestane was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
Time frame: Baseline up to 28 days after last dose
Population: Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug | AEs (All Causalities) | 24 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug | SAEs (All Causalities) | 5 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug | AEs (Treatment Related) | 13 participants |
| Exemestane | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) by Relationship to Study Drug | SAEs (Treatment Related) | 0 participants |
Secondary
Number of Missed Exemestane Doses
Time frame: Week 25, 49, 73, 97, 121, 145
Population: Full analysis set (FAS) included all participants who had received at least 1 dose of exemestane during the observation period. 'N' (number of participants analyzed)=participants evaluable for this measure. n=number of participants evaluable at specified time points. None of the participants were evaluable at Week 145 and hence data not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exemestane | Number of Missed Exemestane Doses | Week 25 (n=18) | 4.9 missed doses | Standard Deviation 7.02 |
| Exemestane | Number of Missed Exemestane Doses | Week 49 (n=8) | 9.6 missed doses | Standard Deviation 20.4 |
| Exemestane | Number of Missed Exemestane Doses | Week 73 (n=5) | 7.6 missed doses | Standard Deviation 12.54 |
| Exemestane | Number of Missed Exemestane Doses | Week 97 (n=4) | 12.3 missed doses | Standard Deviation 13.07 |
| Exemestane | Number of Missed Exemestane Doses | Week 121 (n=4) | 6.3 missed doses | Standard Deviation 0.5 |
Secondary
Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy
Time frame: Baseline up to Year 3
Population: FAS included all participants who had received at least 1 dose of exemestane during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane | Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy | Received hormonal therapy | 4 participants |
| Exemestane | Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy | Received chemotherapy | 319 participants |
| Exemestane | Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy | Received both hormonal and chemotherapy | 1 participants |
| Exemestane | Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy | No hormonal or chemotherapy received | 34 participants |
| Exemestane | Number of Participants Who Received Hormonal Therapy or Chemotherapy After Discontinuation of Exemestane Therapy | Missing or no response | 20 participants |
Secondary
Number of Participants With Reasons for Discontinuing Exemestane Therapy
Time frame: Baseline up to Year 3
Population: Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Adverse event | 10 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Insufficient clinical response | 11 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Did not meet entrance criteria | 9 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Lost to follow-up | 12 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | No longer willing to participate in study | 16 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Other unspecified | 58 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Protocol violation | 33 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Study terminated by sponsor | 197 participants |
| Exemestane | Number of Participants With Reasons for Discontinuing Exemestane Therapy | Withdrawn due to pregnancy | 1 participants |
Secondary
Percentage of Participants Who Discontinued the Exemestane Therapy
Time frame: Baseline up to Year 3
Population: Safety analysis set included all participants who had received at least 1 dose of exemestane during the observation period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane | Percentage of Participants Who Discontinued the Exemestane Therapy | 91.8 percentage of participants |
Secondary
Recurrence-free Survival (RFS)
Recurrence-free survival defined as the time from study inclusion to the first date of documented recurrence, with events defined as: local recurrence, distant recurrence, new primary breast cancer (includes both ipsilateral and contralateral second primaries), or death due to any cause. New primary cancer at sites other than the breast were not considered as recurrence.
Time frame: Baseline up to Year 3
Population: A subgroup of participants from FAS who had documented recurrence was evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane | Recurrence-free Survival (RFS) | 74.357 weeks |
Secondary
Time to Disease Progression (TTP)
Time to disease progression was defined as the time from inclusion to first local or distant recurrence at any site.
Time frame: Baseline up to Year 3
Population: Time to disease progression was considered complementary to RFS and hence, was not analyzed.