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.