To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.

Phase 3

Completed

Conditions: Somatic BRCA1/2 Mutations
HER2-ve Metastatic Breast Cancer
Germline BRCA1/2 Mutations

Interventions: Drug: Olaparib

Registration Number: NCT03286842

Lead Sponsor: AstraZeneca

Brief Summary: This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations.

Detailed Description: The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in patients with confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations. This study will generate additional data to support other olaparib studies, which may help inform and guide clinical practice. Physician defined the progression-free survival (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2 mutations, it is estimated that up to 1400 patients may require screening in order to identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be administered two olaparib 150mg tablets in morning and evening of every day after a light meal. Dose reductions may be required for olaparib treatment related toxicities. Patients should continue to receive study treatment until documented physician-defined disease progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria. A positive benefit/risk profile is expected and no ethical issues are identified from exposing patients to olaparib within the planned clinical study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 256

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Olaparib	Olaparib	Olaparib 150mg tablets administered orally twice daily continuously

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants	At every visit until the earliest of disease progression, death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.

Secondary Outcome Measures

Name	Time	Method
Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants	At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.
Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants	At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.
Overall Survival (OS) in Germline BRCA Mutated Participants	At every visit and until death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.
Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants	At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Screening (Day -28 to Day -1) until post DCO [up to 3 years]	The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.
Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants	At every visit until second progression or death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented
Clinical Response Rate (CRR) in Germline BRCA Mutated Participants	At every visit until disease progression or death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.
Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants	At every visit until disease progression or death or end of study (up to 3 years)	The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.