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

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.

• Authors: Philipp Harter, Toby Johnson, Dominique Berton-Rigaud, Sang-Yoon Park, Michael Friedlander, Josep M Del Campo, Muneaki Shimada, Frédéric Forget, Mansoor R Mirza, Nicoletta Colombo, Claudio Zamagni, John K Chan, Martin Imhof, Thomas J Herzog, Dearbhaile O'Donnell, Florian Heitz, Karen King, Sandy Stinnett, Catherine Barrett, Minesh Jobanputra, Chun-Fang Xu, Andreas du Bois
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 140 Issue 3 Pg. 443-9 (Mar 2016) ISSN: 1095-6859 [Electronic] United States
• PMID: 26740259 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Indazoles
• Pyrimidines
• Sulfonamides
• pazopanib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Asian People (genetics)
• Carcinoma, Ovarian Epithelial
• Disease-Free Survival
• Fallopian Tube Neoplasms (drug therapy, genetics)
• Female
• Genes, BRCA1
• Genes, BRCA2
• Genome-Wide Association Study
• Germ-Line Mutation
• Humans
• Indazoles
• Maintenance Chemotherapy
• Middle Aged
• Neoplasms, Glandular and Epithelial (drug therapy, genetics)
• Ovarian Neoplasms (drug therapy, genetics)
• Peritoneal Neoplasms (drug therapy, genetics)
• Pyrimidines (therapeutic use)
• Sulfonamides (therapeutic use)
• White People (genetics)
• Young Adult