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.

NCT ID: NCT02000622

Last Updated: 2025-08-03

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

302 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-27

Study Completion Date

2025-12-31

Brief Summary

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This open label, randomised, controlled, multi-centre phase III study will assess the efficacy and safety of single agent olaparib vs standard of care based on physician's choice of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2 mutations.

Detailed Description

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Conditions

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Breast Cancer Metastatic BRCA 1 Gene Mutation BRCA 2 Gene Mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Olaparib

Olaparib tablet 300mg bd po

Group Type EXPERIMENTAL

Olaparib

Intervention Type DRUG

Patients will be administered olaparib orally twice daily (bid) 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.

Physician's choice chemotherapy

Capecitabine 2500 mg/m2 d1-14 q 21, or Vinorelbine 30 mg/m2 d1,8 q 21, or Eribulin 1.4 mg/m2 d1,8 q 21

Group Type ACTIVE_COMPARATOR

Physician's choice chemotherapy

Intervention Type DRUG

Investigators will declare one of the following regimens:

* Capecitabine 2500 mg/m2 po daily (divided in 2 doses) x 14 days, repeat every 21 days
* Vinorelbine 30 mg/m2 IV Day 1 and Day 8, repeat every 21 days
* Eribulin 1.4 mg/m2 IV Day 1 and Day 8, repeat every 21 days

Interventions

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Olaparib

Patients will be administered olaparib orally twice daily (bid) 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.

Intervention Type DRUG

Physician's choice chemotherapy

Investigators will declare one of the following regimens:

* Capecitabine 2500 mg/m2 po daily (divided in 2 doses) x 14 days, repeat every 21 days
* Vinorelbine 30 mg/m2 IV Day 1 and Day 8, repeat every 21 days
* Eribulin 1.4 mg/m2 IV Day 1 and Day 8, repeat every 21 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
* Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
* Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting.
* Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed.
* ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
* ECOG performance status 0-1.
* Adequate bone marrow, kidney and liver function.

Exclusion Criteria

* Prior treatment with PARP inhibitor.
* Patients with HER2 positive disease.
* More than 2 prior lines of chemotherapy for metastatic breast cancer.
* Untreated and/or uncontrolled brain metastases.
* Prior malignancy unless curatively treated and disease-free for \> 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed.
* Known HIV (Human Immunodeficiency Virus) infection.
* Pregnant or breast-feeding women.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Myriad Genetic Laboratories, Inc.

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Robson, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan-Kettering Cancer Center, New York

Locations

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San Diego, California, United States

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Santa Rosa, California, United States

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Whittier, California, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Jacksonville, Florida, United States

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Orlando, Florida, United States

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Plantation, Florida, United States

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Columbus, Georgia, United States

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Marietta, Georgia, United States

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Chicago, Illinois, United States

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Niles, Illinois, United States

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Wichita, Kansas, United States

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Lafayette, Louisiana, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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Rochester, Minnesota, United States

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Saint Louis Park, Minnesota, United States

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Jackson, Mississippi, United States

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Columbia, Missouri, United States

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St Louis, Missouri, United States

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Lebanon, New Hampshire, United States

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Commack, New York, United States

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Harrison, New York, United States

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New York, New York, United States

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New York, New York, United States

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Rockville Centre, New York, United States

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Syracuse, New York, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Sayre, Pennsylvania, United States

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Germantown, Tennessee, United States

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Houston, Texas, United States

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Tyler, Texas, United States

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Burlington, Vermont, United States

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Plovdiv, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Vratsa, , Bulgaria

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Chengdu, , China

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Dalian, , China

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Guangzhou, , China

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Hangzhou, , China

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Harbin, , China

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Nanjing, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Tianjin, , China

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Brno, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Caen, , France

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Montpellier, , France

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Rouen, , France

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Strasbourg, , France

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Villejuif, , France

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Nyíregyháza, , Hungary

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Veszprém, , Hungary

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Bologna, , Italy

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Napoli, , Italy

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Padua, , Italy

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Roma, , Italy

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Roma, , Italy

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Rozzano, , Italy

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Chūōku, , Japan

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Chūōku, , Japan

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Fukuoka, , Japan

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Kagoshima, , Japan

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Nagoya, , Japan

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Osaka, , Japan

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Sapporo, , Japan

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Shinagawa-ku, , Japan

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Suita, , Japan

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Estado de México, , Mexico

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Mérida, , Mexico

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Mérida, , Mexico

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Mérida, , Mexico

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México, , Mexico

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San Juan del Río, , Mexico

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Cusco, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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San Borja, , Peru

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Elblag, , Poland

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Gdansk, , Poland

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Grzepnica, , Poland

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Lodz, , Poland

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Tarnobrzeg, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Arkhangelsk, , Russia

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Ivanovo, , Russia

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Moscow, , Russia

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Omsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saransk, , Russia

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Yaroslavl, , Russia

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Cheongju-si, , South Korea

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Daegu, , South Korea

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Incheon, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Córdoba, , Spain

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Granada, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Oviedo, , Spain

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Seville, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Bern, , Switzerland

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Lausanne, , Switzerland

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Zurich, , Switzerland

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Konya, , Turkey (Türkiye)

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Mersin, , Turkey (Türkiye)

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Aberdeen, , United Kingdom

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Colchester, , United Kingdom

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Coventry, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Plymouth, , United Kingdom

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Countries

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United States Bulgaria China Czechia France Hungary Italy Japan Mexico Peru Poland Romania Russia South Korea Spain Switzerland Taiwan Turkey (Türkiye) United Kingdom

References

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Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.

Reference Type DERIVED
PMID: 28578601 (View on PubMed)

Related Links

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Other Identifiers

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2013-005137-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D0819C00003

Identifier Type: -

Identifier Source: org_study_id

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