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

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 JobanputraChun Fang Xu, Andreas Du Bois

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)443-449
Number of pages7
JournalGynecologic Oncology
Volume140
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Fingerprint

Dive into the research topics of 'BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study'. Together they form a unique fingerprint.

Cite this