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BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2016 Mar; Vol. 140 (3), pp. 443-9. Date of Electronic Publication: 2015 Dec 29. - Publication Year :
- 2016
-
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.<br />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.<br />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).<br />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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Asian People genetics
Carcinoma, Ovarian Epithelial
Disease-Free Survival
Female
Genome-Wide Association Study
Humans
Indazoles
Maintenance Chemotherapy
Middle Aged
White People genetics
Young Adult
Antineoplastic Agents therapeutic use
Fallopian Tube Neoplasms drug therapy
Fallopian Tube Neoplasms genetics
Genes, BRCA1
Genes, BRCA2
Germ-Line Mutation
Neoplasms, Glandular and Epithelial drug therapy
Neoplasms, Glandular and Epithelial genetics
Ovarian Neoplasms drug therapy
Ovarian Neoplasms genetics
Peritoneal Neoplasms drug therapy
Peritoneal Neoplasms genetics
Pyrimidines therapeutic use
Sulfonamides therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 140
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 26740259
- Full Text :
- https://doi.org/10.1016/j.ygyno.2015.12.027