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Gynecol Oncol. 2016 Mar;140(3):443-9. doi: 10.1016/j.ygyno.2015.12.027. Epub 2015 Dec 29.

BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study.

Author information

1
Department of Gynecology & Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany. Electronic address: p.harter@gmx.de.
2
GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
3
Institut de Cancérologie de l'Ouest, Centre René Gauducheau, Saint-Herblain, France.
4
National Cancer Center, Goyang, Republic of Korea.
5
The Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia.
6
Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
7
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Nishimachi, Yonago, Japan.
8
Centre Hospitalier de l'Ardenne, Libramont, Belgium.
9
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
10
Gynecologic Oncology, University of Milan-Bicocca and European Institute of Oncology, Milan, Italy.
11
S. Orsola-Malpighi University Hospital, Bologna, Italy.
12
California Pacific and Palo Alto Sutter Cancer Research Institute, San Francisco, CA, USA.
13
Regional Hospital Korneuburg, Medical University of Vienna, Austria.
14
University of Cincinnati Cancer Institute, Cincinnati, OH, USA.
15
All Ireland Cooperative Oncology Research Group, Dublin, Ireland.
16
Department of Gynecology & Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
17
Parexel International, Durham, NC, USA.
18
Novartis Pharma AG, Basel, Switzerland.
19
Biogen Idec, Berkshire, UK.

Abstract

OBJECTIVE:

AGO-OVAR 16 demonstrated that pazopanib maintenance therapy significantly increased progression-free survival (PFS) in patients with ovarian cancer whose disease had not progressed after first-line therapy. In a sub-study, we evaluated the effect of clinically important germline BRCA1 and BRCA2 mutations on PFS.

METHODS:

Of 940 AGO-OVAR 16 participants, 664 had BRCA1/2 exon sequencing data (pazopanib, n=335; placebo, n=329). A Cox model was used to test the association between genetic variants and PFS.

RESULTS:

Ninety-seven of 664 patients (15%) carried clinically important BRCA1/2 mutations (BRCA1/2 carriers: pazopanib 14%, placebo 16%). Median PFS was longer in BRCA1/2 mutation carriers than in BRCA1/2 non-carriers in the placebo arm (30.3 vs 14.1 months, hazard ratio, 0.48; 95% confidence interval [CI]: 0.29-0.78; P=0.0031); a similar non-significant trend was noted with pazopanib (30.2 vs 17.7 months, hazard ratio, 0.64; 95% CI: 0.40-1.03; P=0.069). Among BRCA1/2 non-carriers, PFS was longer for pazopanib-treated patients than placebo-treated patients (17.7 vs 14.1 months, hazard ratio, 0.77; 95% CI: 0.62-0.97; P=0.024). Among BRCA1/2 carriers, there was no significant PFS difference between treatments, although numbers were small (pazopanib, 46; placebo, 51), resulting in a wide CI (hazard ratio, 1.36; 95% CI: 0.66-2.82).

CONCLUSIONS:

Patients with clinically important BRCA1/2 mutations had better prognosis. BRCA1/2 mutation status might be added as strata in future trials in primary ovarian cancer.

KEYWORDS:

GWAS; Germline BRCA mutation; Ovarian cancer; Pazopanib; Progression-free survival

PMID:
26740259
DOI:
10.1016/j.ygyno.2015.12.027
[Indexed for MEDLINE]

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