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Trial record 1 of 1 for:    Olaparib Monotherapy Versus Physicians Choice Chemotherapy | Romania
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Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations. (OlympiAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02000622
Recruitment Status : Active, not recruiting
First Posted : December 4, 2013
Results First Posted : December 22, 2017
Last Update Posted : March 15, 2022
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer Metastatic
BRCA 1 Gene Mutation
BRCA 2 Gene Mutation
Interventions Drug: Olaparib
Drug: Physician's choice chemotherapy
Enrollment 302
Recruitment Details The first patient was enrolled on 27 March 2014 and the last patient on 30 October 2015. Patients were randomized at 125 centres across 19 countries in North America, South America, Europe and Asia.
Pre-assignment Details Screening occurred in 2 parts. Part 1: patients with unknown BRCA status were tested by Myriad. Part 1 screening failures were mostly due to no BRCA1/2 mutation detected. Part 2: patients with a known germline BRCA mutation were screened. 302 patients were randomized.
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 205 97
Completed 36 17
Not Completed 169 80
Reason Not Completed
Withdrawal by Subject             5             7
Lost to Follow-up             4             0
Death             159             73
Withdrawn due to site closure             1             0
Arm/Group Title Olaparib 300 mg bd Chemotherapy Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 205 97 302
Hide Baseline Analysis Population Description
Full analysis set consisting of all randomized patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Age (years) Number Analyzed 205 participants 97 participants 302 participants
44
(22 to 76)
45
(24 to 68)
44
(22 to 76)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 97 participants 302 participants
<50
138
  67.3%
63
  64.9%
201
  66.6%
>=50-<65
56
  27.3%
30
  30.9%
86
  28.5%
>=65
11
   5.4%
4
   4.1%
15
   5.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 97 participants 302 participants
Female
200
  97.6%
95
  97.9%
295
  97.7%
Male
5
   2.4%
2
   2.1%
7
   2.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 97 participants 302 participants
American Indian or Alaska Native
3
   1.5%
1
   1.0%
4
   1.3%
Asian
66
  32.2%
28
  28.9%
94
  31.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.5%
4
   4.1%
5
   1.7%
White
134
  65.4%
63
  64.9%
197
  65.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.5%
1
   1.0%
2
   0.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Global Number Analyzed 205 participants 97 participants 302 participants
BULGARIA
4
   2.0%
4
   4.1%
8
   2.6%
CHINA
32
  15.6%
9
   9.3%
41
  13.6%
CZECH REPUBLIC
11
   5.4%
1
   1.0%
12
   4.0%
FRANCE
5
   2.4%
4
   4.1%
9
   3.0%
HUNGARY
10
   4.9%
0
   0.0%
10
   3.3%
ITALY
17
   8.3%
7
   7.2%
24
   7.9%
JAPAN
15
   7.3%
9
   9.3%
24
   7.9%
KOREA
11
   5.4%
9
   9.3%
20
   6.6%
MEXICO
1
   0.5%
4
   4.1%
5
   1.7%
PERU
3
   1.5%
1
   1.0%
4
   1.3%
POLAND
10
   4.9%
5
   5.2%
15
   5.0%
ROMANIA
1
   0.5%
1
   1.0%
2
   0.7%
RUSSIAN FEDERATION
10
   4.9%
5
   5.2%
15
   5.0%
SPAIN
7
   3.4%
6
   6.2%
13
   4.3%
SWITZERLAND
6
   2.9%
2
   2.1%
8
   2.6%
TAIWAN
1
   0.5%
1
   1.0%
2
   0.7%
TURKEY
8
   3.9%
6
   6.2%
14
   4.6%
UNITED KINGDOM
8
   3.9%
4
   4.1%
12
   4.0%
UNITED STATES
45
  22.0%
19
  19.6%
64
  21.2%
Receptor status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 97 participants 302 participants
ER and/or PgR positive
103
  50.2%
49
  50.5%
152
  50.3%
ER and PgR negative
102
  49.8%
48
  49.5%
150
  49.7%
[1]
Measure Description: ER = oestrogen receptor, PgR = progesterone receptor. All patients were HER2 negative.
Received prior chemotherapy for metastatic breast cancer  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 97 participants 302 participants
Yes
146
  71.2%
69
  71.1%
215
  71.2%
No
59
  28.8%
28
  28.9%
87
  28.8%
Received prior platinum for breast cancer  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 205 participants 97 participants 302 participants
Yes
60
  29.3%
26
  26.8%
86
  28.5%
No
145
  70.7%
71
  73.2%
216
  71.5%
1.Primary Outcome
Title Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)
Hide Description Time from randomisation to the earliest of objective radiological progression or death by any cause in the absence of objective progression. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
7.0
(5.7 to 8.3)
4.2
(2.8 to 4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments Study is sized to provide 90% power to detect a true treatment effect of PFS hazard ratio 0.653.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments A priori threshold for statistical significance (2-sided) is 0.05.
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.43 to 0.80
Estimation Comments Hazard ratio <1 favours olaparib.
2.Secondary Outcome
Title Time to Second Progression or Death (PFS2)
Hide Description Time from randomisation to the earliest of the progression event subsequent to the first objective radiological progression, or death. Second progression may involve any of; objective radiological or symptomatic progression or death. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Symptomatic progression is assessed by investigators based on clinical examination.
Time Frame Second progression status reviewed every 8 weeks following the first objective radiological progression as per investigator assessment. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
13.2
(10.9 to 15.3)
9.3
(7.3 to 10.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0033
Comments PFS2 tested using a multiple testing procedure with a recycling strategy. With 157 PFS2 events, a priori threshold for statistical significance (2-sided) was 0.008.
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.40 to 0.83
Estimation Comments Hazard ratio <1 favours olaparib.
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Time from randomisation until death due to any cause.
Time Frame Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
19.3
(16.7 to 21.8)
19.6
(14.1 to 24.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5665
Comments OS tested using a multiple testing procedure with a recycling strategy. With 140 OS events, a priori threshold for statistical significance (2-sided) was 0.018.
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.63 to 1.29
Estimation Comments Hazard ratio <1 favours olaparib.
4.Secondary Outcome
Title Objective Response Rate (ORR) Using Blinded Independent Central Review (BICR) Data Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)
Hide Description Number of responders according to blinded independent central review (BICR) assessment. Per Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions; Overall Response = CR + PR.
Time Frame Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable For Response (EFR) Analysis Set consisting of all randomised patients with measurable disease at baseline, i.e. at least one measurable target lesion assessed by blinded independent central review (BICR)
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 167 66
Measure Type: Number
Unit of Measure: Participants
100 19
5.Secondary Outcome
Title Adjusted Mean Change in Global Health Status/Quality of Life (QoL) Score From the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)
Hide Description Change from baseline in global health status/quality of life (QoL) score assessed using a mixed model for repeated measures (MMRM) analysis, including all post-baseline global health status/QoL scores up to the latest scheduled visit where at least 20 patients on each treatment arm have a score. Global health status/QoL score is on a scale from 0 to 100. A higher score represents an improved health status/QoL.
Time Frame EORTC QLQ-C30 assessments performed at baseline then every ~6 weeks until objective radiological disease progression. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of Full Analysis Set (FAS) consisting of all randomised patients with an evaluable baseline EORTC QLQ-C30 assessment and at least one evaluable post-baseline assessment
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 191 73
Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
3.9
(1.5 to 6.3)
-3.6
(-8.0 to 0.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments [Not Specified]
Method Mixed Models Analysis
Comments Variables for treatment, visit, treatment-visit interaction, adjusted for baseline global health status/QoL score, baseline score-visit interaction.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
2.5 to 12.4
Estimation Comments Mean difference >0 favours olaparib.
6.Secondary Outcome
Title Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) in Patients Confirmed as Myriad CDx gBRCAm
Hide Description Time from randomisation to the earliest of objective radiological progression or death by any cause in the absence of objective progression. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Assessed in patients with a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).
Time Frame Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Subset of Full Analysis Set (FAS) consisting of all randomised patients who were confirmed as Myriad CDx gBRCAm
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 202 95
Median (95% Confidence Interval)
Unit of Measure: Months
7.4
(5.7 to 8.3)
4.2
(2.8 to 4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.41 to 0.78
Estimation Comments Hazard ratio <1 favours olaparib.
7.Secondary Outcome
Title Overall Survival (OS) at Final OS
Hide Description Time from randomisation until death due to any cause.
Time Frame Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
19.3
(17.2 to 21.6)
17.1
(13.9 to 21.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5131
Comments OS tested using a multiple testing procedure with a recycling strategy. With 192 OS events, a priori threshold for statistical significance was 0.045.
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.66 to 1.23
Estimation Comments Hazard ratio <1 favours olaparib.
8.Secondary Outcome
Title Overall Survival (OS) at Extended OS
Hide Description Time from randomisation until death due to any cause.
Time Frame Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
19.3
(17.2 to 21.6)
17.1
(13.9 to 21.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4167
Comments [Not Specified]
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.67 to 1.18
Estimation Comments Hazard ratio <1 favours olaparib.
9.Other Pre-specified Outcome
Title Time to First Subsequent Cancer Therapy or Death (TFST)
Hide Description Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.
Time Frame Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
9.4
(8.3 to 10.6)
4.2
(3.3 to 5.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments Supportive analysis to PFS.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.24 to 0.47
Estimation Comments Hazard ratio <1 favours olaparib.
10.Other Pre-specified Outcome
Title Time to Second Subsequent Cancer Therapy or Death (TSST)
Hide Description Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.
Time Frame Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
14.3
(12.2 to 15.5)
10.5
(8.4 to 11.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments Supportive analysis to PFS2.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.38 to 0.74
Estimation Comments Hazard ratio <1 favours olaparib.
11.Other Pre-specified Outcome
Title Time to First Subsequent Cancer Therapy or Death (TFST) at Extended OS
Hide Description Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.
Time Frame Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
9.4
(8.3 to 10.6)
4.3
(3.4 to 5.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments Supportive analysis to PFS.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.27 to 0.50
Estimation Comments Hazard ratio <1 favours olaparib.
12.Other Pre-specified Outcome
Title Time to Second Subsequent Cancer Therapy or Death (TSST) at Extended OS
Hide Description Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.
Time Frame Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consisting of all randomised patients
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description:
Olaparib 300 mg bd tablets
Physician's choice of chemotherapy; capecitabine, vinorelbine, or eribulin
Overall Number of Participants Analyzed 205 97
Median (95% Confidence Interval)
Unit of Measure: Months
14.3
(12.3 to 15.7)
10.5
(8.5 to 11.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib 300 mg bd, Chemotherapy
Comments Supportive analysis to PFS2.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Stratified by received prior chemotherapy for metastatic breast cancer (yes/no) and receptor status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.40 to 0.72
Estimation Comments Hazard ratio <1 favours olaparib.
Time Frame Adverse events and serious adverse events were collected throughout the study until study completion (up to a maximum of 30 months). They are reported from date of first dose of study treatment until the earliest of 30 days after last dose of study treatment and data cut-off.
Adverse Event Reporting Description Adverse events and serious adverse events are reported in the Safety Analysis Set including all patients who received at least one dose of study treatment (n=296). Six patients on the chemotherapy arm did not receive any study treatment and therefore are excluded from the Safety Analysis Set, leaving n=91 patients on the chemotherapy arm. All cause mortality is reported in the Full Analysis Set (n=302).
 
Arm/Group Title Olaparib 300 mg bd Chemotherapy
Hide Arm/Group Description Description (Arm-group) Description (Arm-group)
All-Cause Mortality
Olaparib 300 mg bd Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   159/205 (77.56%)      73/97 (75.26%)    
Hide Serious Adverse Events
Olaparib 300 mg bd Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   37/205 (18.05%)      15/91 (16.48%)    
Blood and lymphatic system disorders     
Anaemia † 1  5/205 (2.44%)  7 2/91 (2.20%)  2
Febrile bone marrow aplasia † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Febrile neutropenia † 1  0/205 (0.00%)  0 2/91 (2.20%)  2
Neutropenia † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Thrombocytopenia † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Cardiac disorders     
Atrial fibrillation † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Ear and labyrinth disorders     
Vertigo † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Gastrointestinal disorders     
Ascites † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Diarrhoea † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Nausea † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Vomiting † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
General disorders     
Malaise † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Pyrexia † 1  3/205 (1.46%)  3 0/91 (0.00%)  0
Hepatobiliary disorders     
Bile duct stone † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Immune system disorders     
Drug hypersensitivity † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Infections and infestations     
Appendicitis † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Biliary sepsis † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Cellulitis staphylococcal † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Gastrointestinal infection † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Pneumonia † 1  2/205 (0.98%)  2 0/91 (0.00%)  0
Pyelonephritis † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Sepsis † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Streptococcal sepsis † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Injury, poisoning and procedural complications     
Hip fracture † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Radiation skin injury † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Tibia fracture † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Investigations     
Neutrophil count decreased † 1  2/205 (0.98%)  2 0/91 (0.00%)  0
Platelet count decreased † 1  2/205 (0.98%)  4 0/91 (0.00%)  0
Metabolism and nutrition disorders     
Hypokalaemia † 1  0/205 (0.00%)  0 1/91 (1.10%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Back pain † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Intervertebral disc protrusion † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Vertebral foraminal stenosis † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Nervous system disorders     
Central nervous system lesion † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Epilepsy † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Headache † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Intracranial pressure increased † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Seizure † 1  2/205 (0.98%)  5 0/91 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 1  4/205 (1.95%)  4 0/91 (0.00%)  0
Pleural effusion † 1  1/205 (0.49%)  1 1/91 (1.10%)  1
Pulmonary embolism † 1  1/205 (0.49%)  1 1/91 (1.10%)  1
Skin and subcutaneous tissue disorders     
Dermatitis allergic † 1  1/205 (0.49%)  2 0/91 (0.00%)  0
Vascular disorders     
Aortic aneurysm † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Embolism † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Pelvic venous thrombosis † 1  1/205 (0.49%)  1 0/91 (0.00%)  0
Phlebitis † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
Venous thrombosis † 1  0/205 (0.00%)  0 1/91 (1.10%)  1
1
Term from vocabulary, MedDRA 22.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Olaparib 300 mg bd Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   196/205 (95.61%)      85/91 (93.41%)    
Blood and lymphatic system disorders     
Anaemia † 1  76/205 (37.07%)  129 21/91 (23.08%)  29
Leukopenia † 1  23/205 (11.22%)  55 9/91 (9.89%)  40
Lymphopenia † 1  14/205 (6.83%)  30 1/91 (1.10%)  2
Neutropenia † 1  37/205 (18.05%)  89 27/91 (29.67%)  78
Thrombocytopenia † 1  13/205 (6.34%)  20 5/91 (5.49%)  5
Gastrointestinal disorders     
Abdominal distension † 1  7/205 (3.41%)  7 5/91 (5.49%)  6
Abdominal pain † 1  14/205 (6.83%)  16 6/91 (6.59%)  7
Abdominal pain upper † 1  15/205 (7.32%)  16 5/91 (5.49%)  5
Constipation † 1  26/205 (12.68%)  30 12/91 (13.19%)  13
Diarrhoea † 1  42/205 (20.49%)  68 19/91 (20.88%)  29
Dyspepsia † 1  17/205 (8.29%)  20 4/91 (4.40%)  4
Nausea † 1  119/205 (58.05%)  175 31/91 (34.07%)  40
Stomatitis † 1  16/205 (7.80%)  23 10/91 (10.99%)  10
Vomiting † 1  66/205 (32.20%)  127 13/91 (14.29%)  18
General disorders     
Asthenia † 1  19/205 (9.27%)  28 12/91 (13.19%)  15
Fatigue † 1  61/205 (29.76%)  80 22/91 (24.18%)  23
Mucosal inflammation † 1  5/205 (2.44%)  5 6/91 (6.59%)  7
Pyrexia † 1  27/205 (13.17%)  35 16/91 (17.58%)  20
Infections and infestations     
Influenza † 1  14/205 (6.83%)  15 4/91 (4.40%)  4
Nasopharyngitis † 1  17/205 (8.29%)  26 3/91 (3.30%)  5
Upper respiratory tract infection † 1  27/205 (13.17%)  40 9/91 (9.89%)  16
Urinary tract infection † 1  13/205 (6.34%)  14 3/91 (3.30%)  3
Investigations     
Alanine aminotransferase increased † 1  24/205 (11.71%)  39 16/91 (17.58%)  19
Aspartate aminotransferase increased † 1  20/205 (9.76%)  29 15/91 (16.48%)  19
Gamma-glutamyltransferase increased † 1  13/205 (6.34%)  14 5/91 (5.49%)  5
Neutrophil count decreased † 1  21/205 (10.24%)  49 17/91 (18.68%)  43
Platelet count decreased † 1  10/205 (4.88%)  19 6/91 (6.59%)  10
White blood cell count decreased † 1  33/205 (16.10%)  75 19/91 (20.88%)  40
Metabolism and nutrition disorders     
Decreased appetite † 1  35/205 (17.07%)  41 11/91 (12.09%)  14
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  22/205 (10.73%)  27 9/91 (9.89%)  9
Back pain † 1  29/205 (14.15%)  32 8/91 (8.79%)  9
Musculoskeletal chest pain † 1  11/205 (5.37%)  11 5/91 (5.49%)  5
Musculoskeletal pain † 1  13/205 (6.34%)  13 4/91 (4.40%)  4
Myalgia † 1  8/205 (3.90%)  8 9/91 (9.89%)  10
Pain in extremity † 1  15/205 (7.32%)  19 3/91 (3.30%)  3
Nervous system disorders     
Dizziness † 1  18/205 (8.78%)  18 7/91 (7.69%)  8
Dysgeusia † 1  17/205 (8.29%)  22 6/91 (6.59%)  6
Headache † 1  41/205 (20.00%)  51 14/91 (15.38%)  15
Peripheral sensory neuropathy † 1  3/205 (1.46%)  3 9/91 (9.89%)  10
Psychiatric disorders     
Insomnia † 1  13/205 (6.34%)  14 7/91 (7.69%)  8
Respiratory, thoracic and mediastinal disorders     
Cough † 1  35/205 (17.07%)  40 6/91 (6.59%)  7
Dyspnoea † 1  15/205 (7.32%)  19 9/91 (9.89%)  10
Skin and subcutaneous tissue disorders     
Alopecia † 1  7/205 (3.41%)  8 12/91 (13.19%)  13
Palmar-plantar erythrodysaesthesia syndrome † 1  1/205 (0.49%)  1 19/91 (20.88%)  25
Pruritus † 1  6/205 (2.93%)  6 5/91 (5.49%)  6
1
Term from vocabulary, MedDRA 22.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Science Director
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: clinicaltrialtransparency@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02000622    
Other Study ID Numbers: D0819C00003
2013-005137-20 ( EudraCT Number )
First Submitted: November 18, 2013
First Posted: December 4, 2013
Results First Submitted: November 28, 2017
Results First Posted: December 22, 2017
Last Update Posted: March 15, 2022