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

TitleBRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study.
Publication TypeJournal Article
Year of Publication2016
AuthorsHarter, P, Johnson, T, Berton-Rigaud, D, Park, S-Y, Friedlander, MLeonard, Del Campo, JM, Shimada, M, Forget, F, Mirza, MR, Colombo, N, Zamagni, C, Chan, JK, Imhof, M, Herzog, TJ, O'Donnell, D, Heitz, F, King, K, Stinnett, S, Barrett, C, Jobanputra, M, Xu, C-F, du Bois, A
JournalGynecol Oncol
Volume140
Issue3
Pagination443-9
Date Published2016 Mar
ISSN1095-6859
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 14.1months, 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 17.7months, 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 14.1months, 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.

DOI10.1016/j.ygyno.2015.12.027
Alternate JournalGynecol. Oncol.
PubMed ID26740259