TY - JOUR
T1 - BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study
AU - Harter, Philipp
AU - Johnson, Toby
AU - Berton-Rigaud, Dominique
AU - Park, Sang Yoon
AU - Friedlander, Michael
AU - Del Campo, Josep M.
AU - Shimada, Muneaki
AU - Forget, Frédéric
AU - Mirza, Mansoor R.
AU - Colombo, Nicoletta
AU - Zamagni, Claudio
AU - Chan, John K.
AU - Imhof, Martin
AU - Herzog, Thomas J.
AU - O'Donnell, Dearbhaile
AU - Heitz, Florian
AU - King, Karen
AU - Stinnett, Sandy
AU - Barrett, Catherine
AU - Jobanputra, Minesh
AU - Xu, Chun Fang
AU - Du Bois, Andreas
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Germline BRCA mutation
KW - GWAS
KW - Ovarian cancer
KW - Pazopanib
KW - Progression-free survival
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U2 - 10.1016/j.ygyno.2015.12.027
DO - 10.1016/j.ygyno.2015.12.027
M3 - Article
C2 - 26740259
AN - SCOPUS:84959450892
VL - 140
SP - 443
EP - 449
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 3
ER -