Breast Cancer
Conditions
Keywords
Breast Cancer, Adjuvant, Olaparib, BRCA 1/2, HER2
Brief summary
Olaparib treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy
Detailed description
Patients will be randomised in 1:1 ratio to either olaparib or placebo. Randomisation will be stratified by Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC), prior neoadjuvant versus adjuvant chemotherapy and prior platinum use for breast cancer. Randomised patients will receive study treatment for up to a maximum of 12 months. All patients will have safety assessments every 2 weeks during the first month, every 4 weeks for the following 5 months and 3 monthly for the remaining 6 months of study treatment plus 30 days after its discontinuation. Following randomisation, all patients will be assessed regularly for signs, symptoms and evidence of disease recurrence by taking medical history, physical examination and mammogram/breast MRI. Efficacy assessments will be performed on a 3 monthly basis during the first 2 years, followed by 6 monthly assessments for years 3, 4 and 5 and annually thereafter. All patients (except those with bilateral mastectomy) will have mammogram / breast MRI annually for 10 years beginning 6 months after randomisation. All randomised patients will have clinical assessment visits for 10 years following their randomisation into the study. Once a patient completes 10 years of clinical assessment they will enter the survival follow up phase of the trial which will continue until approximately 10 years after the last patient is randomised.
Interventions
DRUGOlaparib
Patients will be administred olaparib orally twice daily (b.i.d.) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 ml of water
DRUGPlacebo
Patients will be administred matching placebo. Two (2) tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 ml of water
Sponsors
AstraZeneca
Frontier Science & Technology Research Foundation, Inc.
NRG Oncology
Myriad Genetic Laboratories, Inc.
The Breast Adjuvant Study Team
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the following phenotypes: 1. Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative (not eligible for anti-HER2 therapy) 2. ER and/or PgR positive, HER2 negative * Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). * Completed adequate breast and axilla surgery. * Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed. * ECOG 0-1.
Exclusion criteria
* Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment. * Patients with second primary malignancy. EXCEPTIONS are: 1. adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma 2. other solid tumours and lymphomas (without bone marrow involvement) diagnosed ≥ 5 years prior to randomisation and treated with no evidence of disease recurrence and for whom no more than one line of chemotherapy was applied. * Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. * Evidence of metastatic breast cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease Free Survival (IDFS) | From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) | An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant Disease Free Survival (DDFS) | From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) | A DDFS event is defined as documented evidence of first distant recurrence of breast cancer or death from any cause |
| Overall Survival (OS) | From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months) | An OS event is defined as death by any cause. |
| Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | From date of randomisation to data cut off: 05 June 2024 (approximately 10 years 2 months) | Number of patients with contralateral invasive breast cancer, contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. Analysis of contralateral breast cancers exclude patients with a bilateral mastectomy prior to randomisation. Analysis of new primary ovarian cancers excludes male patients and patients with a bilateral oophorectomy prior to randomisation. Analysis of new primary fallopian tube cancer excludes male patients and patients with a bilateral salpingectomy prior to randomisation. Analysis of new primary peritoneal cancers excludes male patients. |
| Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) | Change from baseline for FACIT-Fatigue Score at 6, 12, 18 and 24 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% Confidence Interval (CI) are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue. |
| Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) | Change from baseline for FACIT-Fatigue Score at 6, 12, 18 and 24 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue. |
| Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) | Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6, 12, 18 and 24 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life. |
| Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) | Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6, 12, 18 and 24 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life. |
Countries
Argentina, Australia, Austria, Belgium, Canada, China, France, Germany, Hungary, Iceland, Israel, Italy, Japan, Netherlands, Poland, Portugal, Puerto Rico, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORAndrew Tutt, Doctor of Medicine
Integrated Cancer Centre Guy's Hospital, King's College, London School of Medicine, London, UK
PRINCIPAL_INVESTIGATORJudy Garber, Doctor of Medicine
Harvard Medical School, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Susan F. Smither Center for Women's Cancers, 450 Brookline Avenue, Boston; MA 02215, US
PRINCIPAL_INVESTIGATORCharles Geyer, Doctor of Medicine
Virginia Commonwealth University Massey Cancer Center, McGlothlin Medical Education Center, Room 12-217, 1201 East Marshall St., PO Box 980070, Richmond, VA 23298-0070, USA
Participant flow
Recruitment details
The first patient was enrolled on 22 April 2014. Patients were randomised from 554 centres in 23 countries worldwide.
Pre-assignment details
Patients with unknown germline BRCA (gBRCA) mutation status prior to randomisation underwent Screening Part 1 to ascertain gBRCA mutation status during, or prior to, neoadjuvant/adjuvant chemotherapy. All patients with known gBRCA mutation status (including those found through Screening Part 1) underwent Screening Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Olaparib Olaparib tablets 300mg taken orally twice daily. | 921 |
| Placebo Placebo tablets taken orally twice daily. | 915 |
| Total | 1,836 |
Baseline characteristics
| Characteristic | Olaparib | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 43.0 Years STANDARD_DEVIATION 9.8 | 43.3 Years STANDARD_DEVIATION 10 | 43.6 Years STANDARD_DEVIATION 10.1 |
| Age, Customized 30-39 years | 333 Participants | 639 Participants | 306 Participants |
| Age, Customized <30 years | 51 Participants | 110 Participants | 59 Participants |
| Age, Customized 40-49 years | 315 Participants | 623 Participants | 308 Participants |
| Age, Customized 50-59 years | 166 Participants | 338 Participants | 172 Participants |
| Age, Customized 60-69 years | 48 Participants | 114 Participants | 66 Participants |
| Age, Customized >=70 years | 8 Participants | 12 Participants | 4 Participants |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized ASIAN | 259 Participants | 531 Participants | 272 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 19 Participants | 48 Participants | 29 Participants |
| Race/Ethnicity, Customized HISPANIC OR LATINO | 34 Participants | 58 Participants | 24 Participants |
| Race/Ethnicity, Customized MISSING | 10 Participants | 18 Participants | 8 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized NOT HISPANIC OR LATINO | 805 Participants | 1617 Participants | 812 Participants |
| Race/Ethnicity, Customized NOT KNOWN, NOT RECORDED, OR REFUSED | 82 Participants | 161 Participants | 79 Participants |
| Race/Ethnicity, Customized OTHER | 3 Participants | 9 Participants | 6 Participants |
| Race/Ethnicity, Customized WHITE | 626 Participants | 1225 Participants | 599 Participants |
| Region of Enrollment ARG | 16 Participants | 28 Participants | 12 Participants |
| Region of Enrollment AUS | 30 Participants | 60 Participants | 30 Participants |
| Region of Enrollment AUT | 28 Participants | 53 Participants | 25 Participants |
| Region of Enrollment BEL | 12 Participants | 38 Participants | 26 Participants |
| Region of Enrollment CAN | 11 Participants | 34 Participants | 23 Participants |
| Region of Enrollment CHE | 4 Participants | 21 Participants | 17 Participants |
| Region of Enrollment CHN | 117 Participants | 247 Participants | 130 Participants |
| Region of Enrollment DEU | 106 Participants | 198 Participants | 92 Participants |
| Region of Enrollment ESP | 63 Participants | 109 Participants | 46 Participants |
| Region of Enrollment FRA | 77 Participants | 142 Participants | 65 Participants |
| Region of Enrollment GBR | 60 Participants | 106 Participants | 46 Participants |
| Region of Enrollment HUN | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment ISL | 5 Participants | 6 Participants | 1 Participants |
| Region of Enrollment ISR | 30 Participants | 65 Participants | 35 Participants |
| Region of Enrollment ITA | 30 Participants | 57 Participants | 27 Participants |
| Region of Enrollment JPN | 64 Participants | 140 Participants | 76 Participants |
| Region of Enrollment KOR | 53 Participants | 97 Participants | 44 Participants |
| Region of Enrollment NLD | 11 Participants | 29 Participants | 18 Participants |
| Region of Enrollment POL | 50 Participants | 109 Participants | 59 Participants |
| Region of Enrollment PRT | 7 Participants | 13 Participants | 6 Participants |
| Region of Enrollment SWE | 20 Participants | 35 Participants | 15 Participants |
| Region of Enrollment TWN | 8 Participants | 12 Participants | 4 Participants |
| Region of Enrollment USA | 111 Participants | 220 Participants | 109 Participants |
| Sex: Female, Male Female | 919 Participants | 1830 Participants | 911 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 107 / 921 | 143 / 915 |
| other Total, other adverse events | 794 / 911 | 674 / 904 |
| serious Total, serious adverse events | 79 / 911 | 79 / 904 |
Outcome results
Primary
Invasive Disease Free Survival (IDFS)
An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause.
Time frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Invasive Disease Free Survival (IDFS) | 106 Participants |
| Placebo | Invasive Disease Free Survival (IDFS) | 178 Participants |
p-value: 0.000007399.5% CI: [0.409, 0.816]Log Rank
Secondary
Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy
Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6, 12, 18 and 24 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life.
Time frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021)
Population: Patient reported outcomes (PRO) Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 6 months | -0.5 Scores on a scale |
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 12 months | 0.6 Scores on a scale |
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 18 months | 2.9 Scores on a scale |
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 24 months | 4.5 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 24 months | 4.8 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 6 months | 2.2 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 18 months | 5.1 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 12 months | 3.1 Scores on a scale |
Secondary
Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy
Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6, 12, 18 and 24 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life.
Time frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021)
Population: Patient reported outcomes (PRO) Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 18 months | 3.3 Scores on a scale |
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 6 months | -0.4 Scores on a scale |
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 24 months | 2.8 Scores on a scale |
| Olaparib | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 12 months | 0.5 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 24 months | 6.1 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 18 months | 4.4 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 12 months | 2.7 Scores on a scale |
| Placebo | Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline EORTC QLQ-C30 Global health status score to 6 months | 0.4 Scores on a scale |
Secondary
Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy
Change from baseline for FACIT-Fatigue Score at 6, 12, 18 and 24 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue.
Time frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021)
Population: Patient reported outcomes (PRO) Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 6 months | -0.7 Scores on a scale |
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 12 months | -0.8 Scores on a scale |
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 18 months | 0.9 Scores on a scale |
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 24 months | 1.3 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 24 months | 1.6 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 6 months | 0.6 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 18 months | 1.2 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 12 months | 0.5 Scores on a scale |
Secondary
Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy
Change from baseline for FACIT-Fatigue Score at 6, 12, 18 and 24 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% Confidence Interval (CI) are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue.
Time frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021)
Population: Patient reported outcomes (PRO) Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 6 months | -1.5 Scores on a scale |
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 12 months | -1.5 Scores on a scale |
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 18 months | 1.3 Scores on a scale |
| Olaparib | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 24 months | 1.6 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 24 months | 2.0 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 6 months | -0.2 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 18 months | 1.4 Scores on a scale |
| Placebo | Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy | Change from baseline FACIT-Fatigue Score to 12 months | 0.0 Scores on a scale |
Secondary
Distant Disease Free Survival (DDFS)
A DDFS event is defined as documented evidence of first distant recurrence of breast cancer or death from any cause
Time frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Distant Disease Free Survival (DDFS) | 89 Participants |
| Placebo | Distant Disease Free Survival (DDFS) | 152 Participants |
p-value: 0.000025799.5% CI: [0.392, 0.831]Log Rank
Secondary
Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer
Number of patients with contralateral invasive breast cancer, contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. Analysis of contralateral breast cancers exclude patients with a bilateral mastectomy prior to randomisation. Analysis of new primary ovarian cancers excludes male patients and patients with a bilateral oophorectomy prior to randomisation. Analysis of new primary fallopian tube cancer excludes male patients and patients with a bilateral salpingectomy prior to randomisation. Analysis of new primary peritoneal cancers excludes male patients.
Time frame: From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months)
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olaparib | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | New primary peritoneal cancer | 0 Participants |
| Olaparib | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | Contralateral invasive breast cancer | 19 Participants |
| Olaparib | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | Contralateral non-invasive breast cancer | 2 Participants |
| Olaparib | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | New primary ovarian cancer | 1 Participants |
| Olaparib | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | New primary fallopian tube cancer | 1 Participants |
| Placebo | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | New primary fallopian tube cancer | 4 Participants |
| Placebo | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | New primary ovarian cancer | 5 Participants |
| Placebo | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | Contralateral invasive breast cancer | 21 Participants |
| Placebo | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | New primary peritoneal cancer | 0 Participants |
| Placebo | Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer | Contralateral non-invasive breast cancer | 4 Participants |
Secondary
Overall Survival (OS)
An OS event is defined as death by any cause.
Time frame: From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Overall Survival (OS) | 75 Participants |
| Placebo | Overall Survival (OS) | 109 Participants |
p-value: 0.009198.5% CI: [0.468, 0.973]Log Rank